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Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers
Jae Sik Kim, Joo Ho Lee, Sang-Rok Jeon, Yongsub Kim, Seung Hyuck Jeon, Hong-Gyun Wu
Cancer Res Treat. 2023;55(3):737-745.   Published online January 4, 2023
DOI: https://doi.org/10.4143/crt.2022.1414
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)–overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen.
Materials and Methods
Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription–quantitative polymerase chain reaction.
Results
We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1, and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment.
Conclusion
The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

Citations

Citations to this article as recorded by  
  • Uncovering the bookshelves of CRISPR-based libraries: Advances and applications in cancer studies
    Nathalia Quintero-Ruiz, Wesley de Lima Oliveira, Marcos Vinicius Esteca, Daniela Campos Granato, Fernando Moreira Simabuco
    Critical Reviews in Oncology/Hematology.2024; 196: 104287.     CrossRef
  • CRISPR-Cas and CRISPR-based screening system for precise gene editing and targeted cancer therapy
    Mingming Qin, Chunhao Deng, Liewei Wen, Guoqun Luo, Ya Meng
    Journal of Translational Medicine.2024;[Epub]     CrossRef
  • 5,672 View
  • 278 Download
  • 2 Web of Science
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Paip1 Indicated Poor Prognosis in Cervical Cancer and Promoted Cervical Carcinogenesis
Nan Li, Junjie Piao, Xinyue Wang, Ki-Yeol Kim, Jung Yoon Bae, Xiangshan Ren, Zhenhua Lin
Cancer Res Treat. 2019;51(4):1653-1665.   Published online April 19, 2019
DOI: https://doi.org/10.4143/crt.2018.544
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was aimed to investigate the role of poly(A)-binding protein-interacting protein 1 (Paip1) in cervical carcinogenesis.
Materials and Methods
The expression of Paip1 in normal cervical epithelial tissues and cervical cancer (CC) tissues were detected by immunohistochemistry. In vivo and in vitro assays were performed to validate effect of Paip1 on CC progression.
Results
Paip1 was found to be up-regulated in CC, which was linked with shorter survival. Knockdown of Paip1 inhibited cell growth, induced apoptosis and cell cycle arrest in CC cells, whereas its overexpression reversed these effects. The in vivo tumor model confirmed the pro-tumor role of Paip1 in CC growth.
Conclusion
Altogether, the investigation demonstrated the clinical significance of Paip1 expression, which prompted that the up-regulated of Paip1 can presumably be a potential prognostic and progression marker for CC.

Citations

Citations to this article as recorded by  
  • Prioritizing cervical cancer candidate genes using chaos game and fractal-based time series approach
    T. Mallikarjuna, N. B. Thummadi, Vaibhav Vindal, P. Manimaran
    Theory in Biosciences.2024; 143(3): 183.     CrossRef
  • Knockdown of PAIP1 Inhibits Breast Cancer Cell Proliferation by Regulating Cyclin E2 mRNA Stability
    Wenqing Yang, Qingkun Wang, Qi Li, Yue Han, Yu Zhang, Lu Zhu, Lianhua Zhu, Junjie Piao
    Molecular Carcinogenesis.2024; 63(12): 2392.     CrossRef
  • Human Proteome Microarray identifies autoantibodies to tumor‐associated antigens as serological biomarkers for the diagnosis of hepatocellular carcinoma
    Qian Yang, Hua Ye, Guiying Sun, Keyan Wang, Liping Dai, Cuipeng Qiu, Jianxiang Shi, Jicun Zhu, Xiao Wang, Peng Wang
    Molecular Oncology.2023; 17(5): 887.     CrossRef
  • PAIP1 regulates expression of immune and inflammatory response associated genes at transcript level in liver cancer cell
    Jianfeng Zheng, Weiwei Fan, Xiaoyu Zhang, Weili Quan, Yunfei Wu, Mengni Shu, Moyang Chen, Ming Liang
    PeerJ.2023; 11: e15070.     CrossRef
  • Advances in HPV‐associated tumor management: Therapeutic strategies and emerging insights
    Xiangjin Gong, Hao Chi, Zhijia Xia, Guanhu Yang, Gang Tian
    Journal of Medical Virology.2023;[Epub]     CrossRef
  • Prioritizing the candidate genes related to cervical cancer using the moment of inertia tensor
    Neelesh Babu Thummadi, Mallikarjuna T., Vaibhav Vindal, Manimaran P.
    Proteins: Structure, Function, and Bioinformatics.2022; 90(2): 363.     CrossRef
  • Effect of PAIP1 on the metastatic potential and prognostic significance in oral squamous cell carcinoma
    Neeti Swarup, Kyoung-Ok Hong, Kunal Chawla, Su-Jung Choi, Ji-Ae Shin, Kyu-Young Oh, Hye-Jung Yoon, Jae-Il Lee, Sung-Dae Cho, Seong-Doo Hong
    International Journal of Oral Science.2022;[Epub]     CrossRef
  • CRISPR/Cas9 Screening for Identification of Genes Required for the Growth of Ovarian Clear Cell Carcinoma Cells
    Ayako Kawabata, Tomoatsu Hayashi, Yoko Akasu-Nagayoshi, Ai Yamada, Naomi Shimizu, Naoko Yokota, Ryuichiro Nakato, Katsuhiko Shirahige, Aikou Okamoto, Tetsu Akiyama
    Current Issues in Molecular Biology.2022; 44(4): 1587.     CrossRef
  • Circ_0005576 Exerts an Oncogenic Role in Cervical Cancer via miR-1305-Dependent Regulation of PAIP1
    Yajing Wang, Fang Du, Zongyuan Xie, Junhao Lai, Yuanjie Li, Yongping Xu, Rui Tong
    Reproductive Sciences.2022; 29(9): 2647.     CrossRef
  • The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness
    Vincenzo Salemme, Costanza Angelini, Jennifer Chapelle, Giorgia Centonze, Dora Natalini, Alessandro Morellato, Daniela Taverna, Emilia Turco, Ugo Ala, Paola Defilippi
    Cellular and Molecular Life Sciences.2021; 78(4): 1355.     CrossRef
  • Effects of inducing apoptosis and inhibiting proliferation of siRNA on polyadenylate‐binding protein‐interacting protein 1 in tongue cell carcinoma
    Huixu Xie, Lisa Yang, Qin Hu, Yingqi Song, Xiaoyi Wang, Liming Zhou, Longjiang Li
    Head & Neck.2020; 42(12): 3623.     CrossRef
  • RETRACTED: Inhibition of carnitine palmitoyl transferase 1A-induced fatty acid oxidation suppresses cell progression in gastric cancer
    Liqiang Wang, Changfeng Li, Yumei Song, ZhenKun Yan
    Archives of Biochemistry and Biophysics.2020; 696: 108664.     CrossRef
  • Whole-genome resequencing of Dulong Chicken reveal signatures of selection
    Q. Wang, D. Li, A. Guo, M. Li, L. Li, J. Zhou, S. K. Mishra, G. Li, Y. Duan, Q. Li
    British Poultry Science.2020; 61(6): 624.     CrossRef
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  • 13 Web of Science
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Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro
Hyeon Kang Koh, Soo Yeon Seo, Jin Ho Kim, Hak Jae Kim, Eui Kyu Chie, Seung-Ki Kim, Il Han Kim
Cancer Res Treat. 2019;51(2):696-705.   Published online August 13, 2018
DOI: https://doi.org/10.4143/crt.2018.249
AbstractAbstract PDFPubReaderePub
Purpose
Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect.
Materials and Methods
Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively.
Results
DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells.
Conclusion
Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

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  • The role of KDM4A‐mediated histone methylation on temozolomide resistance in glioma cells through the HUWE1/ROCK2 axis
    Xi‐Xi Li, Jia‐Kun Xu, Wei‐Jie Su, Hong‐Lin Wu, Kun Zhao, Chang‐Ming Zhang, Xiang‐Kun Chen, Li‐Xuan Yang
    The Kaohsiung Journal of Medical Sciences.2024; 40(2): 161.     CrossRef
  • Glioblastoma Therapy: Past, Present and Future
    Elena Obrador, Paz Moreno-Murciano, María Oriol-Caballo, Rafael López-Blanch, Begoña Pineda, Julia Gutiérrez-Arroyo, Alba Loras, Luis Gonzalez-Bonet, Conrado Martinez-Cadenas, José Estrela, María Marqués-Torrejón
    International Journal of Molecular Sciences.2024; 25(5): 2529.     CrossRef
  • Exploring Disulfiram’s Anticancer Potential: PLGA Nano-Carriers for Prolonged Drug Delivery and Potential Improved Therapeutic Efficacy
    Ibrahim Dumbuya, Ana Maria Pereira, Ibrahim Tolaymat, Adnan Al Dalaty, Basel Arafat, Matt Webster, Barbara Pierscionek, Mouhamad Khoder, Mohammad Najlah
    Nanomaterials.2024; 14(13): 1133.     CrossRef
  • Targeting Retinaldehyde Dehydrogenases to Enhance Temozolomide Therapy in Glioblastoma
    Rafael Jiménez, Andrada Constantinescu, Muhube Yazir, Paula Alfonso-Triguero, Raquel Pequerul, Xavier Parés, Mileidys Pérez-Alea, Ana Paula Candiota, Jaume Farrés, Julia Lorenzo
    International Journal of Molecular Sciences.2024; 25(21): 11512.     CrossRef
  • Clinical, pharmacological, and formulation evaluation of disulfiram in the treatment of glioblastoma - a systematic literature review
    Beáta-Mária Benkő, Dimitrios A. Lamprou, Anna Sebestyén, Romána Zelkó, István Sebe
    Expert Opinion on Drug Delivery.2023; 20(4): 541.     CrossRef
  • Effect of Disulfiram and Copper Plus Chemotherapy vs Chemotherapy Alone on Survival in Patients With Recurrent Glioblastoma
    Katja Werlenius, Sara Kinhult, Tora Skeidsvoll Solheim, Henriette Magelssen, David Löfgren, Munila Mudaisi, Sofia Hylin, Jiri Bartek, Michael Strandéus, Magnus Lindskog, Havyan Bahroz Rashid, Louise Carstam, Sasha Gulati, Ole Solheim, Jiri Bartek, Øyvind
    JAMA Network Open.2023; 6(3): e234149.     CrossRef
  • Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways
    Yao Liu, Xin Guan, Meiling Wang, Naixue Wang, Yutong Chen, Baolei Li, Zhuxuan Xu, Fangwei Fu, Cheng Du, Zhendong Zheng
    Bioengineered.2022; 13(3): 6579.     CrossRef
  • Disulfiram in glioma: Literature review of drug repurposing
    Shiyu Zhong, Shengyu Liu, Xin Shi, Xudong Zhang, Kunhang Li, Guojun Liu, Lishuai Li, Shanwei Tao, Bowen Zheng, Weichen Sheng, Ziyin Ye, Qichen Xing, Qingqing Zhai, Lijie Ren, Ying Wu, Yijun Bao
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Multimodal targeting of glioma with functionalized nanoparticles
    Hany E. Marei
    Cancer Cell International.2022;[Epub]     CrossRef
  • Formulation Comprising Arsenic Trioxide and Dimercaprol Enhances Radiosensitivity of Pancreatic Cancer Xenografts
    Renyan Tang, Jianmin Zhu, Ying Liu, Ning Wu, Jinbin Han
    Technology in Cancer Research & Treatment.2021;[Epub]     CrossRef
  • Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells
    Hyeon Ji Kim, Tae-Jun Kim, Yu Gyung Kim, Chaeeun Seong, Jin-Hwa Cho, Wanil Kim, Kyung-Ha Lee, Do-Yeon Kim
    Pharmaceutics.2021; 13(9): 1410.     CrossRef
  • Disulfiram Sensitizes a Therapeutic-Resistant Glioblastoma to the TGF-β Receptor Inhibitor
    Chan-Chuan Liu, Cheng-Lin Wu, Meng-Xuan Lin, Chun-I Sze, Po-Wu Gean
    International Journal of Molecular Sciences.2021; 22(19): 10496.     CrossRef
  • Repurposing Disulfiram for Targeting of Glioblastoma Stem Cells: An In Vitro Study
    Lisa Zirjacks, Nicolai Stransky, Lukas Klumpp, Lukas Prause, Franziska Eckert, Daniel Zips, Sabine Schleicher, Rupert Handgretinger, Stephan M. Huber, Katrin Ganser
    Biomolecules.2021; 11(11): 1561.     CrossRef
  • The combination of disulfiram and copper for cancer treatment
    Hong Li, Jingyu Wang, Chunfu Wu, Lihui Wang, Zhe-Sheng Chen, Wei Cui
    Drug Discovery Today.2020; 25(6): 1099.     CrossRef
  • Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme
    Jinyeong Choi, Gaeun Kim, Su Bin Cho, Hyung-Jun Im
    Journal of Nanobiotechnology.2020;[Epub]     CrossRef
  • Disulfiram as a Therapeutic Agent for Metastatic Malignant Melanoma—Old Myth or New Logos?
    Francisco Meraz-Torres, Sarah Plöger, Claus Garbe, Heike Niessner, Tobias Sinnberg
    Cancers.2020; 12(12): 3538.     CrossRef
  • Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents
    Elmira Ekinci, Sagar Rohondia, Raheel Khan, Qingping P. Dou
    Recent Patents on Anti-Cancer Drug Discovery.2019; 14(2): 113.     CrossRef
  • 9,570 View
  • 297 Download
  • 20 Web of Science
  • 17 Crossref
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Effects and Mechanisms of Metformin on the Proliferation of Esophageal Cancer Cells In Vitro and In Vivo
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Cancer Res Treat. 2017;49(3):778-789.   Published online November 11, 2016
DOI: https://doi.org/10.4143/crt.2015.485
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to observe the effects of metformin on human esophageal cancer cell and to investigate its possible mechanisms.
Materials and Methods
Cell viability was detected by using a Cell Counting Kit-8, while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo. Immunohistochemistry was determined based on the expression of PKM2 and Bim in tumor tissues. Tunnel was used to assess tumor cell apoptosis.
Results
Esophageal cancer cells viability was reduced after metformin treatment. The cell cycle was arrested in the G0/G1 phase, apoptosis was induced, caspase 3 was activated, caspase 9 was downregulated, and the pro-apoptotic protein Bim increased. Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2. Insulin-like growth factor 1 partly reversed metfromin-induced apoptosis and attenuated the repression effect of metfomin to PI3K, pAKT, and PKM2. Knockout PKM2 resulted in the activation of caspase 3, down-regulation of caspase 9, and increased expression of Bim. In the Eca109 xenograft model, metformin significantly reduced tumor growth. Furthermore, we found that metformin treatment increased the rate of apoptosis, down-regulation of PKM2, and up-regulation of Bim in tumor tissues.
Conclusion
Metformin restrained esophageal cancer cell proliferation partly by suppressing the PI3K/AKT/mTOR pathway.

Citations

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  • Metformin and the PI3K/AKT signaling pathway: implications for cancer, cardiovascular, and central nervous system diseases
    Hemin Ashayeri Ahmadabad, Somayeh Mohammadi Panah, Hojat Ghasemnejad‐Berenji, Shabnam Ghojavand, Morteza Ghasemnejad-Berenji, Mohammad Rafi Khezri
    Naunyn-Schmiedeberg's Archives of Pharmacology.2025; 398(2): 1035.     CrossRef
  • SRT3025-loaded cell membrane hybrid liposomes (3025@ML) enhanced anti-tumor activity of Oxaliplatin via inhibiting pyruvate kinase M2 and fatty acid synthase
    Xiaobin Wang, Shulin Li, Zichen Li, Zhuona Lin, Zhifeng Wang
    Lipids in Health and Disease.2025;[Epub]     CrossRef
  • Exploring the Effects of Metformin on the Body via the Urine Proteome
    Yuzhen Chen, Haitong Wang, Minhui Yang, Ziyun Shen, Youhe Gao
    Biomolecules.2025; 15(2): 241.     CrossRef
  • Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes
    Haneen A. Basheer, Nadeem M. Salman, Rami M. Abdullah, Lina Elsalem, Kamyar Afarinkia
    Translational Oncology.2025; 53: 102323.     CrossRef
  • Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights
    Stavros P. Papadakos, Alexandra Argyrou, Vasileios Lekakis, Konstantinos Arvanitakis, Polyxeni Kalisperati, Ioanna E. Stergiou, Ippokratis Konstantinidis, Dimitrios Schizas, Theocharis Koufakis, Georgios Germanidis, Stamatios Theocharis
    International Journal of Molecular Sciences.2024; 25(5): 2978.     CrossRef
  • Ianus Bifrons: The Two Faces of Metformin
    Umberto Goglia, Iderina Hasballa, Claudia Teti, Mara Boschetti, Diego Ferone, Manuela Albertelli
    Cancers.2024; 16(7): 1287.     CrossRef
  • Changes in the expression of cancer- and metastasis-related genes and proteins after metformin treatment under different metabolic conditions in endometrial cancer cells
    Carsten Lange, Jana Brüggemann, Theresa Thüner, Julia Jauckus, Thomas Strowitzki, Ariane Germeyer
    Heliyon.2023; 9(6): e16678.     CrossRef
  • Metformin Induces a Caspase 3-Unrelated Apoptosis in Human Colorectal Cancer Cell Lines HCT116 and SW620
    Bustanur Rosidi, Diana Priyatno, Teguh Pribadi Putra, Irawan Yusuf
    Cancer Management and Research.2023; Volume 15: 475.     CrossRef
  • Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models
    Mirian Galliote Morale, Rodrigo Esaki Tamura, Ileana Gabriela Sanchez Rubio
    Biomolecules.2022; 12(3): 357.     CrossRef
  • Metformin-Induced Heat Shock Protein Family A Member 6 Is a Promising Biomarker of Esophageal Squamous Cell Carcinoma
    Nobufumi Sekino, Masayuki Kano, Sohei Kobayashi, Kentaro Murakami, Haruhito Sakata, Takeshi Toyozumi, Satoshi Endo, Yasunori Matsumoto, Hiroshi Suito, Masahiko Takahashi, Ryota Otsuka, Masaya Yokoyama, Tadashi Shiraishi, Koichiro Okada, Toshiki Kamata, Ta
    Oncology.2022; 100(5): 267.     CrossRef
  • The Role of PKM2 in the Regulation of Mitochondrial Function: Focus on Mitochondrial Metabolism, Oxidative Stress, Dynamic, and Apoptosis. PKM2 in Mitochondrial Function
    Jing Gao, Yuwei Zhao, Tao Li, Xueqi Gan, Haiyang Yu, Daniel Lopez Malo
    Oxidative Medicine and Cellular Longevity.2022; 2022: 1.     CrossRef
  • Association of Common Use Pharmaceuticals in Reducing Risk of Esophageal Adenocarcinoma: A SEER–Medicare Analysis
    Holli A. Loomans-Kropp, Matthew Chaloux, Ellen Richmond, Asad Umar
    Cancer Prevention Research.2021; 14(2): 195.     CrossRef
  • Advances and challenges in the treatment of esophageal cancer
    Shiming He, Jian Xu, Xiujun Liu, Yongsu Zhen
    Acta Pharmaceutica Sinica B.2021; 11(11): 3379.     CrossRef
  • Changes in protein expression due to metformin treatment and hyperinsulinemia in a human endometrial cancer cell line
    Carsten Lange, Amanda Machado Weber, Ronny Schmidt, Christoph Schroeder, Thomas Strowitzki, Ariane Germeyer, Jae-Wook Jeong
    PLOS ONE.2021; 16(3): e0248103.     CrossRef
  • Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats
    Marwa S. Hamza, Eman Ramadan, Salama A. Salama
    Scientific Reports.2021;[Epub]     CrossRef
  • 12-Epi-Napelline Inhibits Leukemia Cell Proliferation via the PI3K/AKT Signaling Pathway In Vitro and In Vivo
    Jia Han, Wei Hou, Bi-qing Cai, Fan Zhang, Jian-cai Tang, Xing Li
    Evidence-Based Complementary and Alternative Medicine.2021; 2021: 1.     CrossRef
  • Photodynamic therapy induces human esophageal carcinoma cell pyroptosis by targeting the PKM2/caspase-8/caspase-3/GSDME axis
    Lisha Li, Dongfeng Song, Ling Qi, Mingxia Jiang, Yiming Wu, Junqing Gan, Kui Cao, Yanjing Li, Yuxian Bai, Tongsen Zheng
    Cancer Letters.2021; 520: 143.     CrossRef
  • Retracted: Silence of cZNF292 suppresses the growth, migration, and invasion of human esophageal cancer Eca‐109 cells via upregulating miR‐206
    Zengjia Liu, Guiju Hu, Yan Zhao, Zuorun Xiao, Mingzhe Yan, Mei Ren
    Journal of Cellular Biochemistry.2020; 121(3): 2354.     CrossRef
  • Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule
    Haoli Wang, Zhilong Zheng, Wen Han, Yuan Yuan, Yao Li, Kailiang Zhou, Qingqing Wang, Ling Xie, Ke Xu, Hongyu Zhang, Huazi Xu, Yanqing Wu, Jian Xiao
    Oxidative Medicine and Cellular Longevity.2020; 2020: 1.     CrossRef
  • The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer
    Mingxia Jiang, Ling Qi, Lisha Li, Yanjing Li
    Cell Death Discovery.2020;[Epub]     CrossRef
  • Metformin delays AKT/c-Met-driven hepatocarcinogenesis by regulating signaling pathways for de novo lipogenesis and ATP generation
    Cong Zhang, Junjie Hu, Lei Sheng, Ming Yuan, Yong Wu, Liang Chen, Guohua Zheng, Zhenpeng Qiu
    Toxicology and Applied Pharmacology.2019; 365: 51.     CrossRef
  • Enhanced penetration and cytotoxicity of metformin and collagenase conjugated gold nanoparticles in breast cancer spheroids
    Elaheh Dalir Abdolahinia, Samad Nadri, Reza Rahbarghazi, Jaleh Barar, Ayoub Aghanejad, Yadollah Omidi
    Life Sciences.2019; 231: 116545.     CrossRef
  • Biguanides Exert Antitumoral Actions in Pituitary Tumor Cells Through AMPK-Dependent and -Independent Mechanisms
    Mari C Vázquez-Borrego, Antonio C Fuentes-Fayos, Aura D Herrera-Martínez, Fernando L-López, Alejandro Ibáñez-Costa, Paloma Moreno-Moreno, María R Alhambra-Expósito, Ana Barrera-Martín, Cristóbal Blanco-Acevedo, Elena Dios, Eva Venegas-Moreno, Juan Soliver
    The Journal of Clinical Endocrinology & Metabolism.2019; 104(8): 3501.     CrossRef
  • Metformin induces TPC-1 cell apoptosis through endoplasmic reticulum stress-associated pathways in vitro and in vivo
    Jianwen Ye, Lei Qi, Kunlun Chen, Renfeng Li, Shengping Song, Chuang Zhou, Wenlong Zhai
    International Journal of Oncology.2019;[Epub]     CrossRef
  • AKT2 contributes to increase ovarian cancer cell migration and invasion through the AKT2-PKM2-STAT3/NF-κB axis
    Bin Zheng, Li Geng, Li Zeng, Fangfang Liu, Qiaojia Huang
    Cellular Signalling.2018; 45: 122.     CrossRef
  • Antitumor effects of metformin are a result of inhibiting nuclear factor kappa B nuclear translocation in esophageal squamous cell carcinoma
    Nobufumi Sekino, Masayuki Kano, Yasunori Matsumoto, Haruhito Sakata, Yasunori Akutsu, Naoyuki Hanari, Kentaro Murakami, Takeshi Toyozumi, Masahiko Takahashi, Ryota Otsuka, Masaya Yokoyama, Tadashi Shiraishi, Koichiro Okada, Isamu Hoshino, Keiko Iida, Aki
    Cancer Science.2018; 109(4): 1066.     CrossRef
  • Down‐regulation of intracellular anti‐apoptotic proteins, particularly c‐FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL
    Ali Hassanzadeh, Majid Farshdousti Hagh, Mohammad Reza Alivand, Ali Akbar Movassaghpour Akbari, Karim Shams Asenjan, Raedeh Saraei, Saeed Solali
    Journal of Cellular Physiology.2018; 233(10): 6470.     CrossRef
  • Interaction Between Prediabetes and the ABO Blood Types in Predicting Postsurgical Esophageal Squamous Cell Carcinoma-Specific Mortality: The FIESTA Study
    Guohui Fan, Dan Hu, Xinran Zhang, Feng Peng, Xiandong Lin, Gang Chen, Binying Liang, Hejun Zhang, Yan Xia, Xiongwei Zheng, Jianzheng Jie, Wenquan Niu
    Frontiers in Oncology.2018;[Epub]     CrossRef
  • Obesity, Diabetes and Gastrointestinal Malignancy: The role of Metformin and other Anti-diabetic Therapy
    McFarlane Samy I
    Global Journal of Obesity, Diabetes and Metabolic Syndrome.2018; : 008.     CrossRef
  • 12,552 View
  • 455 Download
  • 32 Web of Science
  • 29 Crossref
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Induction of Apoptosis in Intestinal Toxicity to a Histone Deacetylase Inhibitor in a Phase I Study with Pelvic Radiotherapy
Erta Kalanxhi, Karianne Risberg, Imon S. Barua, Svein Dueland, Stein Waagene, Solveig Norheim Andersen, Solveig J. Pettersen, Jessica M. Lindvall, Kathrine Røe Redalen, Kjersti Flatmark, Anne Hansen Ree
Cancer Res Treat. 2017;49(2):374-386.   Published online July 28, 2016
DOI: https://doi.org/10.4143/crt.2016.080
AbstractAbstract PDFPubReaderePub
Purpose
When integrating molecularly targeted compounds in radiotherapy, synergistic effects of the systemic agent and radiation may extend the limits of patient tolerance, increasing the demand for understanding the pathophysiological mechanisms of treatment toxicity. In this Pelvic Radiation and Vorinostat (PRAVO) study, we investigated mechanisms of adverse effects in response to the histone deacetylase (HDAC) inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) when administered as a potential radiosensitiser.
Materials and Methods
This phase I study for advanced gastrointestinal carcinoma was conducted in sequential patient cohorts exposed to escalating doses of vorinostat combined with standard-fractionated palliative radiotherapy to pelvic target volumes. Gene expression microarray analysis of the study patient peripheral blood mononuclear cells (PBMC) was followed by functional validation in cultured cell lines and mice treated with SAHA.
Results
PBMC transcriptional responses to vorinostat, including induction of apoptosis, were confined to the patient cohort reporting dose-limiting intestinal toxicities. At relevant SAHA concentrations, apoptotic features (annexin V staining and caspase 3/7 activation, but not poly-(ADP-ribose)-polymerase cleavage) were observed in cultured intestinal epithelial cells. Moreover, SAHA-treated mice displayed significant weight loss.
Conclusion
The PRAVO study design implemented a strategy to explore treatment toxicity caused by an HDAC inhibitor when combined with radiotherapy and enabled the identification of apoptosis as a potential mechanism responsible for the dose-limiting effects of vorinostat. To the best of our knowledge, this is the first report deciphering mechanisms of normal tissue adverse effects in response to an HDAC inhibitor within a combined-modality treatment regimen.

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  • Effect of MicroRNA-210 on the Growth of Ovarian Cancer Cells and the Efficacy of Radiotherapy
    Yinlong Zhao, Shirui Liu, Yu Wen, Lili Zhong
    Gynecologic and Obstetric Investigation.2021; 86(1-2): 71.     CrossRef
  • Valproic Acid Downregulates Cytokine Expression in Human Macrophages Infected with Dengue Virus
    Félix G. Delgado, Paola Cárdenas, Jaime E. Castellanos
    Diseases.2018; 6(3): 59.     CrossRef
  • Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs
    Silmara N. Andrade, Fernanda C. G. Evangelista, Diego Seckler, Deisielly R. Marques, Túlio R. Freitas, Renata R. Nunes, Júlia T. Oliveira, Rosy I. M. A. Ribeiro, Hélio B. Santos, Ralph G. Thomé, Alex G. Taranto, Fabio V. Santos, Gustavo H. R. Viana, Rossi
    Medicinal Chemistry Research.2018; 27(11-12): 2397.     CrossRef
  • Radiosensitization In Vivo by Histone Deacetylase Inhibition with No Increase in Early Normal Tissue Radiation Toxicity
    Blaz Groselj, Jia-Ling Ruan, Helen Scott, Jessica Gorrill, Judith Nicholson, Jacqueline Kelly, Selvakumar Anbalagan, James Thompson, Michael R.L. Stratford, Sarah J. Jevons, Ester M. Hammond, Cheryl L. Scudamore, Martin Kerr, Anne E. Kiltie
    Molecular Cancer Therapeutics.2018; 17(2): 381.     CrossRef
  • 15,363 View
  • 214 Download
  • 4 Web of Science
  • 4 Crossref
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Inhibition of SKP2 Sensitizes Bromocriptine-Induced Apoptosis in Human Prolactinoma Cells
Jinxiang Huang, Fenglin Zhang, Lei Jiang, Guohan Hu, Wei Sun, Chenran Zhang, Xuehua Ding
Cancer Res Treat. 2017;49(2):358-373.   Published online July 28, 2016
DOI: https://doi.org/10.4143/crt.2016.017
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Prolactinoma (prolactin-secreting pituitary adenoma) is one of the most common estrogen-related functional pituitary tumors. As an agonist of the dopamine D2 receptor, bromocriptine is used widely to inhibit prolactinoma progression. On the other hand, it is not always effective in clinical application. Although a dopamine D2 receptor deficiency contributes to the impaired efficiency of bromocriptine therapy to some extent, it is unknown whether there some other underlying mechanisms leading to bromocriptine resistance in prolactinoma treatment. That is the main point addressed in this project.
Materials and Methods
Human prolactinoma samples were used to analyze the S-phase kinase associated protein 2 (SKP2) expression level. Nutlin-3/adriamycin/cisplatin-treated GH3 and MMQ cells were used to analyze apoptosis in SKP2 overexpression or knockdown cells. SKP2 expression and the interaction partners of SKP2 were also detected after a bromocriptine treatment in 293T. Apoptosis was analyzed in C25 and bromocriptine-treated GH3 cells.
Results
Compared to normal pituitary samples, most prolactinoma samples exhibit higher levels of SKP2 expression, which could inhibit apoptosis in a p53-dependent manner. In addition, the bromocriptine treatment prolonged the half-life of SKP2 and resulted in SKP2 overexpression to a greater extent, which in turn compromised its pro-apoptotic effect. As a result, the bromocriptine treatment combined with C25 (a SKP2 inhibitor) led to the maximal apoptosis of human prolactinoma cells.
Conclusion
These findings indicated that SKP2 inhibition sensitized the prolactinoma cells to bromocriptine and helped promote apoptosis. Moreover, a combined treatment of bromocriptine and C25 may contribute to the maximal apoptosis of human prolactinoma cells.

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    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Bortezomib exerts its anti-cancer activity through the regulation of Skp2/p53 axis in non-melanoma skin cancer cells and C. elegans
    Kirti S. Prabhu, Fareed Ahmad, Shilpa Kuttikrishnan, Rari Leo, Tayyiba Akbar Ali, Mahmoud Izadi, Jericha M. Mateo, Majid Alam, Aamir Ahmad, Ammira S. Al-Shabeeb Akil, Ajaz A. Bhat, Joerg Buddenkotte, Ehsan Pourkarimi, Martin Steinhoff, Shahab Uddin
    Cell Death Discovery.2024;[Epub]     CrossRef
  • Prenatal p25-activated Cdk5 induces pituitary tumorigenesis through MCM2 phosphorylation-mediated cell proliferation
    Yingwei Huang, Qiqi Wang, Weiwei Zhou, Yawei Jiang, Kai He, Wei Huang, Yating Feng, Hong Wu, Lijuan Liu, Yue Pan, Yihua Huang, Zirui Chen, Wei Li, Yaowei Huang, Guanchuan Lin, Yulong Zhang, Yongyan Ren, Kaibiao Xu, Yanlin Yu, Yuping Peng, Xinghua Pan, Suy
    Neoplasia.2024; 57: 101054.     CrossRef
  • N-Myc transcriptionally activates Skp2 to suppress p27 expression in small cell lung cancer
    Juntao Zou, Yang Lin, Min Hu, Mengzhi Wan, Xinyu Tan, Xinping Xu, Fei Xu
    Pathology - Research and Practice.2022; 238: 154083.     CrossRef
  • Targeting the Hippo Pathway in Prostate Cancer: What’s New?
    Kelly Coffey
    Cancers.2021; 13(4): 611.     CrossRef
  • Emerging Roles of SKP2 in Cancer Drug Resistance
    Ting Wu, Xinsheng Gu, Hongmei Cui
    Cells.2021; 10(5): 1147.     CrossRef
  • ZNF703 is Overexpressed in Papillary Thyroid Carcinoma Tissues and Mediates K1 Cell Proliferation
    Xiaolin Yang, Geling Liu, Luyang Zang, Ding Li, Fang Yu, Xiuxiu Xiang, Weijuan Li
    Pathology & Oncology Research.2020; 26(1): 355.     CrossRef
  • Skp2 in the ubiquitin‐proteasome system: A comprehensive review
    Moges Dessale Asmamaw, Ying Liu, Yi‐Chao Zheng, Xiao‐Jing Shi, Hong‐Min Liu
    Medicinal Research Reviews.2020; 40(5): 1920.     CrossRef
  • Genomic and molecular characterization of pituitary adenoma pathogenesis: review and translational opportunities
    Mazin Elsarrag, Parantap D. Patel, Ajay Chatrath, Davis Taylor, John A. Jane
    Neurosurgical Focus.2020; 48(6): E11.     CrossRef
  • PGAM5-CypD pathway is involved in bromocriptine-induced RIP3/MLKL-dependent necroptosis of prolactinoma cells
    Shun-Li Zhang, Hai-Bin Tang, Jin-Tao Hu, Zhen-Le Zang, Xiao Ding, Song Li, Hui Yang
    Biomedicine & Pharmacotherapy.2019; 111: 638.     CrossRef
  • Role and mechanisms of a three-dimensional bioprinted microtissue model in promoting proliferation and invasion of growth-hormone-secreting pituitary adenoma cells
    Jinfu Diao, Chuanbao Zhang, Dainan Zhang, Xiong Wang, Jing Zhang, Cheng Ma, Kunxue Deng, Tao Jiang, Wang Jia, Tao Xu
    Biofabrication.2019; 11(2): 025006.     CrossRef
  • Skp2 inhibitor SKPin C1 decreased viability and proliferation of multiple myeloma cells and induced apoptosis
    Ying Yang, Wei Yan, Zhuogang Liu, Minjie Wei
    Brazilian Journal of Medical and Biological Research.2019;[Epub]     CrossRef
  • Dysregulated expression of SKP2 and its role in hematological malignancies
    Michal Kulinski, Iman W. Achkar, Mohammad Haris, Said Dermime, Ramzi M. Mohammad, Shahab Uddin
    Leukemia & Lymphoma.2018; 59(5): 1051.     CrossRef
  • The prolactin‐release inhibitor paeoniflorin suppresses proliferation and induces apoptosis in prolactinoma cells via the mitochondria‐dependent pathway
    Yuanyi Wei, Xia Zhou, Liying Ren, Chunxia Wang, Yuhao Li
    Journal of Cellular Biochemistry.2018; 119(7): 5704.     CrossRef
  • Relation among Aromatase P450 and Tumoral Growth in Human Prolactinomas
    María García-Barrado, Enrique Blanco, María Iglesias-Osma, Marta Carretero-Hernández, Leonardo Catalano-Iniesta, Virginia Sanchez-Robledo, Manuel Carretero, Julio Herrero, Sixto Carrero, José Carretero
    International Journal of Molecular Sciences.2017; 18(11): 2299.     CrossRef
  • 18,226 View
  • 241 Download
  • 16 Web of Science
  • 15 Crossref
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Studying the Effect of Downregulating Autophagy-Related Gene LC3 on TLR3 Apoptotic Pathway Mediated by dsRNA in Hepatocellular Carcinoma Cells
Guilan Wang, Maona Zhang, Yunlong Li, Jiaming Zhou, Li Chen
Cancer Res Treat. 2017;49(1):230-245.   Published online June 13, 2016
DOI: https://doi.org/10.4143/crt.2015.506
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to examine the role of the double-stranded RNA (dsRNA) activated Toll–interleukin-1 receptor domain-containing adaptor inducing interferon β (TRIF) signal pathway in triggering apoptosis in hepatocellular carcinoma (HCC) cells.
Materials and Methods
First, siRNA targeted autophagy–related gene LC3 (pU6H1-LC3 siRNA and siLC3) and a dsRNA used as a Toll-like receptor 3 (TLR3) ligand was constructed and synthesized, respectively. Then, a human HCC cell line was transfected with dsRNA, siLC3, and cotransfected with siLC3 and dsRNA (siLC3+dsRNA), respectively. Finally, quantification real-time polymerase chain reaction, western blotting, and immunofluorescence staining were used in the HCC line (SMMC7721), and MTT assay, flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling, and transmission electron microscopy were used in an HCC xenograft model of nude mice. Human umbilical vein endothelial cell tube forming assay, color Doppler ultrasonographic flow image examination, and CD34-positive microvessel density were used in vitro and in vivo.
Results
Compared with untreated cells, the protein and mRNA expression of TLR3 and TRIF was up-regulated, in order, siLC3+dsRNA, dsRNA, and siLC3. Expression of LC3 was obviously down-regulated and the autophagosomes were significantly decreased in siLC3+dsRNA and siLC3, whereas in dsRNA (p < 0.05). LC3 and TRIF colocation was observed in HepG2 cells. Decreased cell viability, increased apoptosis, decrease in xenograft tumor volume, and angiogenesis potential were also observed in order (p < 0.05).
Conclusion
Suppression of intracellular autophagy resulted in decreased degradation of TRIF protein, which can promote triggering of apoptosis by the TLR3-TRIF pathway. dsRNA and siLC3 could play anticancer roles in coordination.

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  • A Multi-Omics Analysis of a Mitophagy-Related Signature in Pan-Cancer
    Nora Agir, Ilias Georgakopoulos-Soares, Apostolos Zaravinos
    International Journal of Molecular Sciences.2025; 26(2): 448.     CrossRef
  • The Functional Mechanisms of Toll-Like Receptor 3 and Its Implications in Digestive System Tumors
    Bin Han, Chao Zhang, Xiaoxiao Wang, Huangqin Song, Lei Zhang, Tao Li, Jiefeng He, Haoliang Zhao
    Frontiers in Bioscience-Landmark.2023;[Epub]     CrossRef
  • The Role of Autophagy in Liver Cancer: Crosstalk in Signaling Pathways and Potential Therapeutic Targets
    Jianzhou Cui, Han-Ming Shen, Lina Hsiu Kim Lim
    Pharmaceuticals.2020; 13(12): 432.     CrossRef
  • MiR-219a-5p enhances cisplatin sensitivity of human non-small cell lung cancer by targeting FGF9
    Chuangzhou Rao, Xiaobo Miao, Guofang Zhao, Chen Zhang, Haibo Shen, Caijun Dong, Minglei Yang
    Biomedicine & Pharmacotherapy.2019; 114: 108662.     CrossRef
  • Up-regulation of miR-146a increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J
    Lin Shi, Zhaozhong Xu, Gang Wu, Xiaoting Chen, Yuanyuan Huang, Yanjing Wang, Weiqiang Jiang, Bin Ke
    BMC Cancer.2017;[Epub]     CrossRef
  • 14,535 View
  • 181 Download
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Tumor Growth Suppression and Enhanced Radioresponse by an Exogenous Epidermal Growth Factor in Mouse Xenograft Models with A431 Cells
Yu Jin Lim, Sang-Rok Jeon, Jae Moon Koh, Hong-Gyun Wu
Cancer Res Treat. 2015;47(4):921-930.   Published online January 7, 2015
DOI: https://doi.org/10.4143/crt.2014.153
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate whether an exogenous epidermal growth factor (EGF) could induce anti-tumor and radiosensitizing effects in vivo.
Materials and Methods
BALB/c-nu mice that were inoculated with A431 (human squamous cell carcinoma) cells in the right hind legs were divided into five groups: I (no treatment), II (EGF for 6 days), III (EGF for 20 days), IV (radiotherapy [RT]), and V (RT plus concomitant EGF). EGF was administered intraperitoneally (5 mg/kg) once a day and the RT dose was 30 Gy in six fractions. Hematoxylin and eosin (H&E) stained sections of tumor, liver, lung, and kidney tissues were investigated. Additionally, tumors were subjected to immunohistochemistry staining with caspase-3.
Results
EGF for 6 days decreased tumor volume, but it approached the level of the control group at the end of follow-up (p=0.550). The duration of tumor shrinkage was prolonged in group V while the slope of tumor re-growth phase was steeper in group IV (p=0.034). EGF for 20 days decreased tumor volume until the end of the observation period (p < 0.001). Immunohistochemistry revealed that mice in group V showed stronger intensity than those in group IV. There were no abnormal histological findings upon H&E staining of the normal organs.
Conclusion
EGF-induced anti-tumor effect was ascertained in the xenograft mouse models with A431 cells. Concomitant use of EGF has the potential role as a radiosensitizer in the design of fractionated irradiation.

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  • Receptor Elimination by E3 Ubiquitin Ligase Recruitment (REULR): A Targeted Protein Degradation Toolbox
    Dirk H. Siepe, Lora K. Picton, K. Christopher Garcia
    ACS Synthetic Biology.2023; 12(4): 1081.     CrossRef
  • Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers
    Jae Sik Kim, Joo Ho Lee, Sang-Rok Jeon, Yongsub Kim, Seung Hyuck Jeon, Hong-Gyun Wu
    Cancer Research and Treatment.2023; 55(3): 737.     CrossRef
  • DNA damage alters EGFR signaling and reprograms cellular response via Mre-11
    Yael Volman, Ruth Hefetz, Eithan Galun, Jacob Rachmilewitz
    Scientific Reports.2022;[Epub]     CrossRef
  • Efficacy of combined icotinib and pemetrexed in EGFR mutant lung adenocarcinoma cell line xenografts
    Jiadong Cui, Yan Zhang, Di Su, Tao Li, Yu Li
    Thoracic Cancer.2018; 9(9): 1156.     CrossRef
  • Biased signaling downstream of epidermal growth factor receptor regulates proliferative versus apoptotic response to ligand
    Remah Ali, Wells Brown, Stephen Connor Purdy, V. Jo Davisson, Michael K. Wendt
    Cell Death & Disease.2018;[Epub]     CrossRef
  • The paradoxical functions of EGFR during breast cancer progression
    Remah Ali, Michael K Wendt
    Signal Transduction and Targeted Therapy.2017;[Epub]     CrossRef
  • Efficacy of radiotherapy for the treatment of cystic echinococcosis in naturally infected sheep
    Rui Mao, Wen-Bao Zhang, Hong-Zhi Qi, Tao Jiang, Ge Wu, Peng-Fei Lu, Abudula Ainiwaer, Ge Shang, Lin Xu, Jie Hao, Xi Shou, Hai-Tao Li, Jun Li, Song-An Zhang, Yong-Xing Bao, Hao Wen
    Infectious Diseases of Poverty.2017;[Epub]     CrossRef
  • Epidermal Growth Factor Enhances Cellular Uptake of Polystyrene Nanoparticles by Clathrin-Mediated Endocytosis
    Le Phuc, Akiyoshi Taniguchi
    International Journal of Molecular Sciences.2017; 18(6): 1301.     CrossRef
  • 16,213 View
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A Novel, Potent, Small Molecule AKT Inhibitor Exhibits Efficacy against Lung Cancer Cells In Vitro
Saketh S. Dinavahi, Rajagopalan Prasanna, Sriram Dharmarajan, Yogeeswari Perumal, Srikant Viswanadha
Cancer Res Treat. 2015;47(4):913-920.   Published online January 2, 2015
DOI: https://doi.org/10.4143/crt.2014.057
AbstractAbstract PDFPubReaderePub
Purpose
Anomalies of Akt regulation, including overexpression in lung cancer, impart resistance to conventional chemotherapy and radiation, thereby implicating this kinase as a therapeutic intervention point. A novel scaffold of Akt inhibitors was developed through virtual screening of chemical databases available at Birla Institute of Technology and Science, Pilani, Hyderabad, based on docking studies using Maestro. A benzothienopyrimidine derivative (BIA-6) was identified as a potential lead molecule that inhibited Akt1 enzyme activity with an IC50 of 256 nM.
Materials and Methods
BIA-6 was tested for in vitro Akt1 inhibition using a fluorescence resonance energy transfer kit. Anti-proliferative activity was tested in NCI-H460, A549, NCI-H1975, and NCI-H2170 cell lines. The effect of the compound on p-Akt (S473) was estimated.
Results
BIA-6 allosterically caused a dose dependent reduction of growth of cell lines with a half maximal growth inhibition (GI50) range of 0.49 μM to 6.6 μM. Cell cycle analysis indicated that BIA-6 caused a G1 phase arrest at < 100 nM but led to apoptosis at higher doses. BIA- 6 also exhibited synergism with standard chemotherapeutic agents.
Conclusion
BIA-6 is a novel, allosteric Akt inhibitor with potent anti-cancer activity in lung cancer cell lines, that effectively blocks the phosphoinositide-3 kinase/Akt pathway with a high margin selectivity towards normal cells.

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  • Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development
    Saketh S. Dinavahi, Yu-Chi Chen, Raghavendra Gowda, Pavan Kumar Dhanyamraju, Kishore Punnath, Dhimant Desai, Arthur Berg, Scot R. Kimball, Shantu Amin, Jin-Ming Yang, Gavin P. Robertson
    International Journal of Molecular Sciences.2022; 23(7): 3481.     CrossRef
  • Targeting WEE1/AKT Restores p53-Dependent Natural Killer–Cell Activation to Induce Immune Checkpoint Blockade Responses in “Cold” Melanoma
    Saketh S. Dinavahi, Yu-Chi Chen, Kishore Punnath, Arthur Berg, Meenhard Herlyn, Momeneh Foroutan, Nicholas D. Huntington, Gavin P. Robertson
    Cancer Immunology Research.2022; 10(6): 757.     CrossRef
  • Development of a Novel Multi-Isoform ALDH Inhibitor Effective as an Antimelanoma Agent
    Saketh S. Dinavahi, Raghavendra Gowda, Krishne Gowda, Christopher G. Bazewicz, Venkat R. Chirasani, Madhu Babu Battu, Arthur Berg, Nikolay V. Dokholyan, Shantu Amin, Gavin P. Robertson
    Molecular Cancer Therapeutics.2020; 19(2): 447.     CrossRef
  • Screening of Pleural Mesothelioma Cell Lines for Kinase Activity May Identify New Mechanisms of Therapy Resistance in Patients Receiving Platin-Based Chemotherapy
    Sabrina Borchert, Pia-Maria Suckrau, Michael Wessolly, Elena Mairinger, Balazs Hegedus, Thomas Hager, Thomas Herold, Wildfried E. E. Eberhardt, Jeremias Wohlschlaeger, Clemens Aigner, Agnes Bankfalvi, Kurt Werner Schmid, Robert F. H. Walter, Fabian D. Mai
    Journal of Oncology.2019; 2019: 1.     CrossRef
  • Moving Synergistically Acting Drug Combinations to the Clinic by Comparing Sequential versus Simultaneous Drug Administrations
    Saketh S. Dinavahi, Mohammad A. Noory, Raghavendra Gowda, Joseph J. Drabick, Arthur Berg, Rogerio I. Neves, Gavin P. Robertson
    Molecular Pharmacology.2018; 93(3): 190.     CrossRef
  • Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces cell cycle arrest and apoptosis via the downregulation of Akt in human lung cancer cells
    HYUN SOOK LIM, YONG JUNG KANG, BOKYUNG SUNG, SEON HEE KIM, MIN JEONG KIM, HYE RIM KIM, SEONG JIN KIM, YUNG HYUN CHOI, HYUNG RYONG MOON, HAE YOUNG CHUNG, NAM DEUK KIM
    Oncology Reports.2015; 34(5): 2431.     CrossRef
  • 14,827 View
  • 122 Download
  • 6 Web of Science
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Synergistic Effect of Sulindac and Simvastatin on Apoptosis in Lung Cancer A549 Cells through AKT-Dependent Downregulation of Survivin
Young-Suk Kim, Chang-Hwan Seol, Jae-Wan Jung, Su-Jin Oh, Ki-Eun Hwang, Hwi-Jung Kim, Eun-Taik Jeong, Hak-Ryul Kim
Cancer Res Treat. 2015;47(1):90-100.   Published online October 27, 2014
DOI: https://doi.org/10.4143/crt.2013.194
AbstractAbstract PDFPubReaderePub
Purpose
Non-steroidal anti-inflammatory drugs (NSAIDs) and statins are potential chemopreventive or chemotherapeutic agents. The mechanism underlying the deregulation of survivin by NSAIDs and statins in human non-small cell lung cancer cells has not been elucidated. In this study, we investigated the synergistic interaction of sulindac and simvastatin in lung cancer A549 cells.
Materials and Methods
Cell viability was measured by an MTT assay, while the expression of apoptotic markers, AKT, and survivin in response to sulindac and simvastatin was examined by Western blotting. DNA fragmentation by apoptosis was analyzed by flow cytometry in A549 cells. Reactive oxygen species (ROS) generation was measured by flow cytometry using H2DCFDA and MitoSOX Red, and the effects of pretreatment with N-acetylcysteine were tested. The effects of AKT on survivin expression in sulindac- and simvastatin-treated cells were assessed. Survivin was knocked down or overexpressed to determine its role in apoptosis induced by sulindac and simvastatin.
Results
Sulindac and simvastatin synergistically augmented apoptotic activity and intracellular ROS production in A549 cells. Inhibition of AKT by siRNA or LY294002 inhibited survivin, while AKT overexpression markedly increased survivin expression, even in the presence of sulindac and simvastatin. Moreover, survivin siRNA enhanced sulindac- and simvastatininduced apoptosis. In contrast, survivin upregulation protected against sulindac- and simvastatin-induced apoptosis.
Conclusion
Combined treatment with sulindac and simvastatin augmented their apoptotic potential in lung cancer cells through AKT signaling-dependent downregulation of survivin. These results indicate that sulindac and simvastatin may be clinically promising therapies for the prevention of lung cancer.

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  • Regulatory effects of statins on Akt signaling for prevention of cancers
    Fatemeh Sadat Hosseini, Abdolreza Ahmadi, Prashant Kesharwani, Hossein Hosseini, Amirhossein Sahebkar
    Cellular Signalling.2024; 120: 111213.     CrossRef
  • Sulindac exhibits anti-proliferative and anti-invasive effects in uterine serous carcinoma cells
    Shuning Chen, Weimin Kong, Xiaochang Shen, Boer Deng, Jennifer Haag, Nikita Sinha, Catherine John, Wenchuan Sun, Chunxiao Zhou, Victoria L. Bae-Jump
    Journal of Cancer Research and Clinical Oncology.2024;[Epub]     CrossRef
  • BAPST. A Combo of Common Use Drugs as Metabolic Therapy for Cancer: A Theoretical Proposal
    Adriana Romo-Perez, Guadalupe Dominguez-Gomez, Alma Chavez-Blanco, Lucia Taja-Chayeb, Aurora Gonzalez-Fierro, Elisa Garcia-Martinez, Jose Correa-Basurto, Alfonso Duenas-Gonzalez
    Current Molecular Pharmacology.2022; 15(6): 815.     CrossRef
  • Cholesterol-Lowering Drugs on Akt Signaling for Prevention of Tumorigenesis
    Navneet Kumar, Chandi C. Mandal
    Frontiers in Genetics.2021;[Epub]     CrossRef
  • Small molecules regulating reactive oxygen species homeostasis for cancer therapy
    Junmin Zhang, Dongzhu Duan, Zi‐Long Song, Tianyu Liu, Yanan Hou, Jianguo Fang
    Medicinal Research Reviews.2021; 41(1): 342.     CrossRef
  • Lanthanum(III) and neodymium(III) complexes with anti-inflammatory drug sulindac: Synthesis, characterization, thermal investigation using coupled techniques TG-FTIR, and in vitro biological studies
    Renan B. Guerra, Thais Fernanda de Campos Fraga-Silva, Julia Aguiar, Paula B. Oshiro, Bruno B.C. Holanda, James Venturini, Gilbert Bannach
    Inorganica Chimica Acta.2020; 503: 119408.     CrossRef
  • A remarkable in vitro cytotoxic, cell cycle arresting and proapoptotic characteristics of low-dose mixed micellar simvastatin combined with alendronate sodium
    Sandip A. Bandgar, Namdeo R. Jadhav, Arehalli S. Manjappa
    Drug Delivery and Translational Research.2020; 10(4): 1122.     CrossRef
  • Repositioning of drugs for intervention in tumor progression and metastasis: Old drugs for new targets
    Giridhar Mudduluru, Wolfgang Walther, Dennis Kobelt, Mathias Dahlmann, Christoph Treese, Yehuda G. Assaraf, Ulrike Stein
    Drug Resistance Updates.2016; 26: 10.     CrossRef
  • Simvastatin Reduces Cancerogenic Potential of Renal Cancer Cells via Geranylgeranyl Pyrophosphate and Mevalonate Pathway
    Mathias Woschek, Niels Kneip, Katrin Jurida, Ingo Marzi, Borna Relja
    Nutrition and Cancer.2016; 68(3): 420.     CrossRef
  • Celecoxib and sulindac inhibit TGF-β1-induced epithelial-mesenchymal transition and suppress lung cancer migration and invasion via downregulation of sirtuin 1
    Byong-Ki Cha, Young-Suk Kim, Ki-Eun Hwang, Kyung-Hwa Cho, Seon-Hee Oh, Byoung-Ryun Kim, Hong-Young Jun, Kwon-Ha Yoon, Eun-Taik Jeong, Hak-Ryul Kim
    Oncotarget.2016; 7(35): 57213.     CrossRef
  • Ultra-structure changes and survivin expression in uterine fibroids after radiofrequency ablation
    Shan-rong Shu, Xin Luo, Wen-Xia Song, Pei-Wen Chen
    International Journal of Hyperthermia.2015; 31(8): 896.     CrossRef
  • 15,371 View
  • 127 Download
  • 15 Web of Science
  • 11 Crossref
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Radiation-Induced Autophagy Contributes to Cell Death and Induces Apoptosis Partly in Malignant Glioma Cells
Guk Heui Jo, Oliver Bögler, Yong-Joon Chwae, Heon Yoo, Seung Hoon Lee, Jong Bae Park, Youn-Jae Kim, Jong Heon Kim, Ho-Shin Gwak
Cancer Res Treat. 2015;47(2):221-241.   Published online August 29, 2014
DOI: https://doi.org/10.4143/crt.2013.159
AbstractAbstract PDFPubReaderePub
Purpose
Radiation-induced autophagy has been shown to play two different roles, in malignant glioma (MG) cells, cytocidal or cytoprotective. However, neither the role of radiation-induced autophagy for cell death nor the existence of autophagy-induced apoptosis, a well-known cell-death pathway after irradiation, has been verified yet. Materials and Methods We observed both temporal and dose-dependent response patterns of autophagy and apoptosis to radiation in MG cell lines. Additionally, we investigated the role of autophagy in apoptosis through knockdown of autophagy-related proteins. Results Autophagic activity measured by staining of acidic vesicle organelles and Western blotting of LC-3 protein increased in proportion to radiation dose from day 1 to 5 after irradiation. Apoptosis measured by annexin-V staining and Western blotting of cleaved poly(ADP-ribose) polymerase demonstrated relatively late appearance 3 days after irradiation that increased for up to 7 days. Blocking of pan-caspase (Z-VAD-FMK) did not affect apoptosis after irradiation, but silencing of Atg5 effectively reduced radiation-induced autophagy, which decreased apoptosis significantly. Inhibition of autophagy in Atg5 knockdown cells was shown to be beneficial for cell survival. Stable transfection of GFP-LC3 cells was observed after irradiation. Annexin-V was localized in cells bearing GFP-LC3 punctuated spots, indicating autophagy in immunofluorescence. Some of these punctuated GFP-LC3 bearing cells formed conglomerated spots and died in final phase. Conclusion These findings suggest that autophagy appears earlier than apoptosis after irradiation and that a portion of the apoptotic population that appears later is autophagy-dependent. Thus, autophagy is a pathway to cell death after irradiation of MG cells.

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    Mozhdeh Zamani, Erfan Sadeghi, Pooneh Mokarram, Behnam Kadkhodaei, Hadi Ghasemi
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  • Autophagy in glioblastoma: A mechanistic perspective
    Durgesh Meena, Sushmita Jha
    International Journal of Cancer.2024; 155(4): 605.     CrossRef
  • Autophagy is the main driver of radioresistance of HNSCC cells in mild hypoxia
    Rhianna M. Hill, Chun Li, Jonathan R. Hughes, Sonia Rocha, Gabrielle J. Grundy, Jason L. Parsons
    Journal of Cellular and Molecular Medicine.2024;[Epub]     CrossRef
  • The reversibility of cancer radioresistance: a novel potential way to identify factors contributing to tumor radioresistance
    Yoshikazu Kuwahara, Kazuo Tomita, Mehryar Habibi Roudkenar, Amaneh Mohammadi Roushandeh, Tomoaki Sato, Akihiro Kurimasa
    Human Cell.2023; 36(3): 963.     CrossRef
  • The role of autophagy in hypoxia-induced radioresistance
    Rhianna Mae Hill, Matthew Fok, Gabrielle Grundy, Jason Luke Parsons, Sonia Rocha
    Radiotherapy and Oncology.2023; 189: 109951.     CrossRef
  • Caffeine Inhibits Growth of Temozolomide-Treated Glioma via Increasing Autophagy and Apoptosis but Not via Modulating Hypoxia, Angiogenesis, or Endoplasmic Reticulum Stress in Rats
    Jin-Cherng Chen, Juen-Haur Hwang
    Nutrition and Cancer.2022; 74(3): 1090.     CrossRef
  • ABT-737, a BH3 Mimetic, Enhances the Therapeutic Effects of Ionizing Radiation in K-ras Mutant Non-Small Cell Lung Cancer Preclinical Model
    Jung Mo Lee, Hey Soo Kim, Arum Kim, Yoon Soo Chang, Jin Gu Lee, Jaeho Cho, Eun Young Kim
    Yonsei Medical Journal.2022; 63(1): 16.     CrossRef
  • Gambogenic Acid Inhibits Basal Autophagy of Drug-Resistant Hepatoma Cells and Improves Its Sensitivity to Adriamycin
    Meng Wang, Fan Zhan, Hui Cheng, Qinglin Li
    Biological and Pharmaceutical Bulletin.2022; 45(1): 63.     CrossRef
  • Of the many cellular responses activated by TP53, which ones are critical for tumour suppression?
    Annabella F. Thomas, Gemma L. Kelly, Andreas Strasser
    Cell Death & Differentiation.2022; 29(5): 961.     CrossRef
  • Alterations in Molecular Profiles Affecting Glioblastoma Resistance to Radiochemotherapy: Where Does the Good Go?
    Juliana B. Vilar, Markus Christmann, Maja T. Tomicic
    Cancers.2022; 14(10): 2416.     CrossRef
  • Repurposing autophagy regulators in brain tumors
    Edgar Petrosyan, Jawad Fares, Alex Cordero, Aida Rashidi, Víctor A. Arrieta, Deepak Kanojia, Maciej S. Lesniak
    International Journal of Cancer.2022; 151(2): 167.     CrossRef
  • Crosstalk between HSPA5 arginylation and sequential ubiquitination leads to AKT degradation through autophagy flux
    Hyo Jeong Kim, Sun-Yong Kim, Dae-Ho Kim, Joon Seong Park, Seong Hyun Jeong, Young Won Choi, Chul-Ho Kim
    Autophagy.2021; 17(4): 961.     CrossRef
  • Deciphering the Role of Autophagy in Treatment of Resistance Mechanisms in Glioblastoma
    Imran Khan, Mohammad Hassan Baig, Sadaf Mahfooz, Moniba Rahim, Busra Karacam, Elif Burce Elbasan, Ilya Ulasov, Jae-June Dong, Mustafa Aziz Hatiboglu
    International Journal of Molecular Sciences.2021; 22(3): 1318.     CrossRef
  • Therapy-Induced Tumor Cell Death: Friend or Foe of Immunotherapy?
    Thijs A. van Schaik, Kok-Siong Chen, Khalid Shah
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Friend or Foe: Paradoxical Roles of Autophagy in Gliomagenesis
    Don Carlo Ramos Batara, Moon-Chang Choi, Hyeon-Uk Shin, Hyunggee Kim, Sung-Hak Kim
    Cells.2021; 10(6): 1411.     CrossRef
  • Breaking Bad: Autophagy Tweaks the Interplay Between Glioma and the Tumor Immune Microenvironment
    Yuxiang Fan, Yubo Wang, Jian Zhang, Xuechao Dong, Pu Gao, Kai Liu, Chengyuan Ma, Gang Zhao
    Frontiers in Immunology.2021;[Epub]     CrossRef
  • Stat1 confers sensitivity to radiation in cervical cancer cells by controlling Parp1 levels: a new perspective for Parp1 inhibition
    Giuseppina Raspaglio, Marianna Buttarelli, Flavia Filippetti, Alessandra Battaglia, Alexia Buzzonetti, Giovanni Scambia, Daniela Gallo
    Cell Death & Disease.2021;[Epub]     CrossRef
  • HMGB1 mediated autophagy protects glioblastoma cells from carbon-ion beam irradiation injury
    Runhong Lei, Liben Yan, Yulin Deng, Jin Xu, Tuo Zhao, M. Umer Farooq Awan, Qiang Li, Guangming Zhou, Xiao Wang, Hong Ma
    Acta Astronautica.2020; 166: 628.     CrossRef
  • Autophagy as a Potential Therapy for Malignant Glioma
    Angel Escamilla-Ramírez, Rosa A. Castillo-Rodríguez, Sergio Zavala-Vega, Dolores Jimenez-Farfan, Isabel Anaya-Rubio, Eduardo Briseño, Guadalupe Palencia, Patricia Guevara, Arturo Cruz-Salgado, Julio Sotelo, Cristina Trejo-Solís
    Pharmaceuticals.2020; 13(7): 156.     CrossRef
  • Nano delivery of natural substances as prospective autophagy modulators in glioblastoma
    Srishti Agarwal, Toru Maekawa
    Nanomedicine: Nanotechnology, Biology and Medicine.2020; 29: 102270.     CrossRef
  • Elucidation of gastrointestinal dysfunction in response to irradiation using metabolomics
    Mohammed Salah, Saki Osuga, Makiko Nakahana, Yasuhiro Irino, Masakazu Shinohara, Yasuyuki Shimizu, Naritoshi Mukumoto, Hiroaki Akasaka, Ai Nakaoka, Daisuke Miyawaki, Takeaki Ishihara, Kenji Yoshida, Yoshiaki Okamoto, Ryohei Sasaki
    Biochemistry and Biophysics Reports.2020; 23: 100789.     CrossRef
  • The Roles of Autophagy and Senescence in the Tumor Cell Response to Radiation
    Nipa H. Patel, Sahib S. Sohal, Masoud H Manjili, J. Chuck Harrell, David A. Gewirtz
    Radiation Research.2020; 194(2): 103.     CrossRef
  • Dexamethasone Interferes with Autophagy and Affects Cell Survival in Irradiated Malignant Glioma Cells
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    Journal of Korean Neurosurgical Society.2020; 63(5): 566.     CrossRef
  • Inhibition of Endoplasmic Reticulum Stress-Mediated Autophagy Enhances the Anticancer Effect of Iodine-125 Seed Radiation on Esophageal Squamous Cell Carcinoma
    Chao Wang, Tian-Kuan Li, Chu-Hui Zeng, Jian Yang, Yong Wang, Jian Lu, Guang-Yu Zhu, Jin-He Guo
    Radiation Research.2020; 194(3): 236.     CrossRef
  • Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors
    Qin Xia, Mengchuan Xu, Pei Zhang, Liqun Liu, Xinyi Meng, Lei Dong
    Frontiers in Oncology.2020;[Epub]     CrossRef
  • Molecular Insights into the Multifunctional Role of Natural Compounds: Autophagy Modulation and Cancer Prevention
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    Biomedicines.2020; 8(11): 517.     CrossRef
  • High LC3/Beclin Expression Correlates with Poor Survival in Glioma: a Definitive Role for Autophagy as Evidenced by In Vitro Autophagic Flux
    Padmakrishnan CJ, Easwer HV, Vinod Vijayakurup, Girish R Menon, Suresh Nair, Srinivas Gopala
    Pathology & Oncology Research.2019; 25(1): 137.     CrossRef
  • Epsilon-Globin HBE1 Enhances Radiotherapy Resistance by Down-Regulating BCL11A in Colorectal Cancer Cells
    Sang Yoon Park, Seon-Jin Lee, Hee Jun Cho, Jong-Tae Kim, Hyang Ran Yoon, Kyung Ho Lee, Bo Yeon Kim, Younghee Lee, Hee Gu Lee
    Cancers.2019; 11(4): 498.     CrossRef
  • NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line
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    International Journal of Molecular Sciences.2019; 20(12): 3010.     CrossRef
  • Dual functionalized liposomes for efficient co-delivery of anti-cancer chemotherapeutics for the treatment of glioblastoma
    Sushant Lakkadwala, Bruna dos Santos Rodrigues, Chengwen Sun, Jagdish Singh
    Journal of Controlled Release.2019; 307: 247.     CrossRef
  • Glioblastoma: Targeting the autophagy in tumorigenesis
    Kang Yang, Long Niu, Yijing Bai, Weidong Le
    Brain Research Bulletin.2019; 153: 334.     CrossRef
  • Radiotherapy of meningioma: a treatment in need of radiobiological research
    Valentina Pinzi, Ilaria Bisogno, Francesco Prada, Emilio Ciusani, Laura Fariselli
    International Journal of Radiation Biology.2018; 94(7): 621.     CrossRef
  • Radiation, inflammation and the immune response in cancer
    Kelly J. McKelvey, Amanda L. Hudson, Michael Back, Tom Eade, Connie I. Diakos
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  • Association between radiation-induced cell death and clinically relevant radioresistance
    Yoshikazu Kuwahara, Kazuo Tomita, Yusuke Urushihara, Tomoaki Sato, Akihiro Kurimasa, Manabu Fukumoto
    Histochemistry and Cell Biology.2018; 150(6): 649.     CrossRef
  • Autophagic and Apoptotic Pathways as Targets for Chemotherapy in Glioblastoma
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    International Journal of Molecular Sciences.2018; 19(12): 3773.     CrossRef
  • Effects of ionizing radiation on the viability and proliferative behavior of the human glioblastoma T98G cell line
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    Oncology Letters.2018;[Epub]     CrossRef
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    International Journal of Molecular Sciences.2017; 18(6): 1297.     CrossRef
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    Oncology Reports.2017; 37(5): 2994.     CrossRef
  • BAMBI overexpression together with β-sitosterol ameliorates NSCLC via inhibiting autophagy and inactivating TGF-β/Smad2/3 pathway
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    Oncology Reports.2017; 37(5): 3046.     CrossRef
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    International Journal of Molecular Sciences.2017; 18(9): 2001.     CrossRef
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    Oncology Letters.2017; 13(2): 857.     CrossRef
  • To live or let die: Unclear task of autophagy in the radiosensitization battle
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  • Cell intrinsic and extrinsic activators of the unfolded protein response in cancer: Mechanisms and targets for therapy
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    International Journal of Molecular Sciences.2015; 16(11): 26880.     CrossRef
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Synergistic Effect of COX-2 Inhibitor on Paclitaxel-Induced Apoptosis in the Human Ovarian Cancer Cell Line OVCAR-3
Hee Jung Kim, Ga Won Yim, Eun Ji Nam, Young Tae Kim
Cancer Res Treat. 2014;46(1):81-92.   Published online January 15, 2014
DOI: https://doi.org/10.4143/crt.2014.46.1.81
AbstractAbstract PDFPubReaderePub
PURPOSE
Celecoxib, a highly selective cyclooxygenase-2 inhibitor, regulates apoptosis of several types of human cancer cells. The purpose of this study was to investigate whether celecoxib in combination with paclitaxel modulates apoptosis of ovarian cancer cells, and to identify the signal pathway by which celecoxib mediates apoptosis.
MATERIALS AND METHODS
OVCAR-3 cells were exposed to paclitaxel (20 microM) in the absence or presence of celecoxib (10 microM). Cell viability was evaluated using a Cell Counting Kit-8 assay. Apoptosis was evaluated using Annexin-V/7-aminoactinomycin D staining and a cellular DNA fragmentation enzyme-linked immunosorbent assay. Caspase-3, -9, and cleavage of poly ADP-ribose polymerase (PARP) were determined by western blotting. Expression of nuclear factor-kappaB (NF-kappaB) and vascular endothelial growth factor (VEGF) and Akt activation were assessed using reverse transcriptase-polymerase chain reaction and western blotting.
RESULTS
Celecoxib enhanced paclitaxel-induced growth inhibition of OVCAR-3 cells. Celecoxib significantly increased paclitaxel-induced apoptosis of OVCAR-3 cells. Pretreatment with celecoxib also increased activation of caspase-9, -3 and cleaved PARP following paclitaxel-treatment. Exposure of OVCAR-3 cells to celecoxib in combination with paclitaxel resulted in downregulation of NF-kappaB activation and VEGF expression. Furthermore, combining celecoxib and paclitaxel inhibited phosphorylation of Akt.
CONCLUSION
OVCAR-3 cells were sensitized to paclitaxel-induced apoptosis by celecoxib through downregulation of NF-kappaB and Akt activation, suggesting that celecoxib may work synergistically with paclitaxel to inhibit different targets and ultimately produce anticancer effects. Combining celecoxib with paclitaxel may prove beneficial in the clinical treatment of ovarian cancer.

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  • Concomitant effects of paclitaxel and celecoxib on genes involved in apoptosis of triple-negative metastatic breast cancer cells
    Mohaddeseh Hedayat, Mohammad Rafi Khezri, Reza Jafari, Hassan Malekinejad, Naime Majidi Zolbanin
    Medical Oncology.2023;[Epub]     CrossRef
  • Hyperforin-mediated anticancer mechanisms in MDA-MB-231 cell line: insights into apoptotic mediator modulation and caspase activation
    Muttiah Barathan, Ahmad Khusairy Zulpa, Kumutha Malar Vellasamy, Zaridatul Aini Ibrahim, See Mee Hoong, Vanitha Mariappan, Gopinath Venkatraman, Jamuna Vadivelu
    Journal of Taibah University for Science.2023;[Epub]     CrossRef
  • Celecoxib Reverse Invasion and Metastasis of Gastric Cancer through Lnc_AC006548.28-miR-223-LAMC2 Pathway
    Guohua Jin, Jianguang Zhang, Tingting Cao, He Zhu, Yang Shi, Kapil Sharma
    Computational Intelligence and Neuroscience.2022; 2022: 1.     CrossRef
  • New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways
    Alma Martelli, Marzieh Omrani, Maryam Zarghooni, Valentina Citi, Simone Brogi, Vincenzo Calderone, Antoni Sureda, Shahrokh Lorzadeh, Simone C. da Silva Rosa, Beniamin Oscar Grabarek, Rafał Staszkiewicz, Marek J. Los, Seyed Fazel Nabavi, Seyed Mohammad Nab
    Cancers.2022; 14(23): 5839.     CrossRef
  • MicroRNA-758 Regulates Oral Squamous Cell Carcinoma via COX-2
    Gang Dong, Hong Chen, Yan Shi, Chunrong Jiang, Hongtao Yang
    Indian Journal of Surgery.2021; 83(4): 932.     CrossRef
  • Synergistic effects of green tea extract and paclitaxel in the induction of mitochondrial apoptosis in ovarian cancer cell lines
    Mohammad Panji, Vahideh Behmard, Zahra Zare, Monireh Malekpour, Hasan Nejadbiglari, Saeede Yavari, Tina Nayerpour dizaj, Azadeh Safaeian, Ali Bakhshi, Omid Abazari, Mojtaba Abbasi, Parisa Khanicheragh, Maryam Shabanzadeh
    Gene.2021; 787: 145638.     CrossRef
  • Spike-in normalization for single-cell RNA-seq reveals dynamic global transcriptional activity mediating anticancer drug response
    Xin Wang, Jane Frederick, Hongbin Wang, Sheng Hui, Vadim Backman, Zhe Ji
    NAR Genomics and Bioinformatics.2021;[Epub]     CrossRef
  • Identification of Key Genes and Pathways Associated With Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis
    Zhimin Shen, Mingduan Chen, Fei Luo, Hui Xu, Peipei Zhang, Jihong Lin, Mingqiang Kang
    Frontiers in Genetics.2021;[Epub]     CrossRef
  • Cyclooxygenase-2 promotes ovarian cancer cell migration and cisplatin resistance via regulating epithelial mesenchymal transition
    Lin Deng, Ding-qing Feng, Bin Ling
    Journal of Zhejiang University-SCIENCE B.2020; 21(4): 315.     CrossRef
  • Paclitaxel induces apoptosis through the TAK1–JNK activation pathway
    Di Yu‐Wei, Zhuo‐sheng Li, Shu‐min Xiong, Ge Huang, Yan‐fei Luo, Tie‐ying Huo, Mao‐hua Zhou, You‐wei Zheng
    FEBS Open Bio.2020; 10(8): 1655.     CrossRef
  • Integration of genetic variants and gene network for drug repurposing in colorectal cancer
    Lalu Muhammad Irham, Henry Sung-Ching Wong, Wan-Hsuan Chou, Wirawan Adikusuma, Eko Mugiyanto, Wan-Chen Huang, Wei-Chiao Chang
    Pharmacological Research.2020; 161: 105203.     CrossRef
  • Correlation between the changes of serum COX 2, APE1, VEGF, TGF-β and TSGF levels and prognosis in patients with osteosarcoma before and after treatment
    Qingxi Zhang, Guo Dong, Fuchuan Wang, Wenyuan Ding
    Journal of Cancer Research and Therapeutics.2020; 16(2): 335.     CrossRef
  • Preventative effect of celecoxib in dimethylbenz[a]anthracene-induced ovarian cancer in rats
    Zhuyan Shao, Qiang Wen, Tao Zhu, Wei Jiang, Yu Kang, Conjian Xu, Shihua Wang
    Archives of Gynecology and Obstetrics.2018; 298(5): 981.     CrossRef
  • Cyclooxygenase-1 (COX-1) and COX-1 Inhibitors in Cancer: A Review of Oncology and Medicinal Chemistry Literature
    Alessandra Pannunzio, Mauro Coluccia
    Pharmaceuticals.2018; 11(4): 101.     CrossRef
  • Targeting multidrug-resistant ovarian cancer through estrogen receptor α dependent ATP depletion caused by hyperactivation of the unfolded protein response
    Xiaobin Zheng, Neal Andruska, Michael J. Lambrecht, Sisi He, Amadeo Parissenti, Paul J. Hergenrother, Erik R. Nelson, David J. Shapiro
    Oncotarget.2018; 9(19): 14741.     CrossRef
  • MicroRNA-381 regulates the occurrence and immune responses of coronary atherosclerosis via cyclooxygenase-2
    Kaiyou Song, Lianting Li, Guiling Sun, Yanjin Wei
    Experimental and Therapeutic Medicine.2018;[Epub]     CrossRef
  • Cyclooxygenase-2 mediated synergistic effect of ursolic acid in combination with paclitaxel against human gastric carcinoma
    Xian Xu, Guo-Qin Zhu, Kai Zhang, Yi-Chan Zhou, Xiao-Lin Li, Wei Xu, Hao Zhang, Yun Shao, Zhen-Yu Zhang, Wei-Hao Sun
    Oncotarget.2017; 8(54): 92770.     CrossRef
  • Literature-based discovery of new candidates for drug repurposing
    Hsih-Te Yang, Jiun-Huang Ju, Yue-Ting Wong, Ilya Shmulevich, Jung-Hsien Chiang
    Briefings in Bioinformatics.2016; : bbw030.     CrossRef
  • Synergistic growth inhibitory effect of deracoxib with doxorubicin against a canine mammary tumor cell line, CMT-U27
    Tülay BAKIREL, Fulya Üstün ALKAN, Oya ÜSTÜNER, Suzan ÇINAR, Funda YILDIRIM, Gaye ERTEN, Utku BAKIREL
    Journal of Veterinary Medical Science.2016; 78(4): 657.     CrossRef
  • Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer
    Andrew J. Wilson, Oluwole Fadare, Alicia Beeghly-Fadiel, Deok-Soo Son, Qi Liu, Shilin Zhao, Jeanette Saskowski, Md. Jashim Uddin, Cristina Daniel, Brenda Crews, Brian D. Lehmann, Jennifer A. Pietenpol, Marta A. Crispens, Lawrence J. Marnett, Dineo Khabele
    Oncotarget.2015; 6(25): 21353.     CrossRef
  • 13,223 View
  • 120 Download
  • 25 Web of Science
  • 20 Crossref
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The Blocking of c-Met Signaling Induces Apoptosis through the Increase of p53 Protein in Lung Cancer
Hae-Yun Jung, Hyun-Jung Joo, Jong Kuk Park, Yeul Hong Kim
Cancer Res Treat. 2012;44(4):251-261.   Published online December 31, 2012
DOI: https://doi.org/10.4143/crt.2012.44.4.251
AbstractAbstract PDFPubReaderePub
PURPOSE
c-Met is an attractive potential target for novel therapeutic inhibition of human cancer, and c-Met tyrosine kinase inhibitors (TKIs) are effective growth inhibitors of various malignancies. However, their mechanisms in anticancer effects are not clear. In the present study, we investigated the possibility that blocking c-Met signaling induces p53-mediated growth inhibition in lung cancer.
MATERIALS AND METHODS
The growth inhibitory effects of c-Met TKI (SU11274) on lung cancer cells and a xenograft model were assessed using the MTT assay, flow cytometry, and terminal deoxyribonucleotide transferase-mediated nick-end labeling staining. The role of p53 protein in the sensitivity of c-Met TKI (SU11274) was examined by Western blot analysis and immunohistochemistry.
RESULTS
SU11274 significantly induced apoptosis in A549 cells with wild-type p53, compared with that in Calu-1 cells with null-type p53. SU11274 increased p53 protein by enhancing the stability of p53 protein. Increased p53 protein by SU11274 induced up-regulation of Bax and PUMA expression and down-regulation of Bcl-2 expression, subsequently activating caspase 3. In p53 knock-out and knock-in systems, we confirmed that SU11274 caused apoptosis through the p53-mediated apoptotic pathway. Likewise, in the A549 xenograft model, SU11274 effectively shrank tumor volume and induced apoptosis via increased p53 protein expression. Blocking c-Met signaling increased the level of p53 protein.
CONCLUSION
Our finding suggested that p53 plays an important role in SU11274-induced apoptosis, and p53 status seems to be related to the sensitivity to SU11274 in lung cancer.

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  • Fragment-based design and synthesis of coumarin-based thiazoles as dual c-MET/STAT-3 inhibitors for potential antitumor agents
    Bassem H. Naguib, Heba A. Elsebaie, Mohamed S. Nafie, Samy Mohamady, Nader R. Albujuq, Aya Samir Ayed, Dina Nada, Ahmed F. Khalil, Salma M. Hefny, Haytham O. Tawfik, Moataz A. Shaldam
    Bioorganic Chemistry.2024; 151: 107682.     CrossRef
  • A Boolean Model of the Proliferative Role of the lncRNA XIST in Non-Small Cell Lung Cancer Cells
    Shantanu Gupta, Daner A. Silveira, Ronaldo F. Hashimoto, Jose Carlos M. Mombach
    Biology.2022; 11(4): 480.     CrossRef
  • Artonin F Induces the Ubiquitin-Proteasomal Degradation of c-Met and Decreases Akt-mTOR Signaling
    Rapeepun Soonnarong, Ismail Dwi Putra, Nicharat Sriratanasak, Boonchoo Sritularak, Pithi Chanvorachote
    Pharmaceuticals.2022; 15(5): 633.     CrossRef
  • Targeted inhibition of c-MET by podophyllotoxin promotes caspase-dependent apoptosis and suppresses cell growth in gefitinib-resistant non-small cell lung cancer cells
    Ha-Na Oh, Ah-Won Kwak, Mee-Hyun Lee, Eunae Kim, Goo Yoon, Seung-Sik Cho, Kangdong Liu, Jung-Il Chae, Jung-Hyun Shim
    Phytomedicine.2021; 80: 153355.     CrossRef
  • Identification of four methylation-driven genes as candidate biomarkers for monitoring single-walled carbon nanotube-induced malignant transformation of the lung
    Dongli Xie, Xiaogang Luo
    Toxicology and Applied Pharmacology.2021; 412: 115391.     CrossRef
  • Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer
    Fatemeh Moosavi, Elisa Giovannetti, Godefridus J. Peters, Omidreza Firuzi
    Critical Reviews in Oncology/Hematology.2021; 160: 103234.     CrossRef
  • Pharmacological inhibition of the MEK5/ERK5 and PI3K/Akt signaling pathways synergistically reduces viability in triple‐negative breast cancer
    Thomas D. Wright, Christopher Raybuck, Akshita Bhatt, Darlene Monlish, Suravi Chakrabarty, Katy Wendekier, Nathan Gartland, Mohit Gupta, Matthew E. Burow, Patrick T. Flaherty, Jane E. Cavanaugh
    Journal of Cellular Biochemistry.2020; 121(2): 1156.     CrossRef
  • The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells
    Ibraheem M. Attafi, Saleh A. Bakheet, Hesham M. Korashy
    Toxicology Mechanisms and Methods.2020; 30(3): 197.     CrossRef
  • Folic acid-conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action
    Khaled AbouAitah, Anna Swiderska-Sroda, Ahmed A. Farghali, Jacek Wojnarowicz, Agata Stefanek, Stanislaw Gierlotka, Agnieszka Opalinska, Abdou K. Allayeh, Tomasz Ciach, Witold Lojkowski
    Oncotarget.2018; 9(41): 26466.     CrossRef
  • Genetic association analysis of the RTK/ERK pathway with aggressive prostate cancer highlights the potential role of CCND2 in disease progression
    Yang Chen, Qin Zhang, Qiuyan Wang, Jie Li, Csilla Sipeky, Jihan Xia, Ping Gao, Yanling Hu, Haiying Zhang, Xiaobo Yang, Haitao Chen, Yonghua Jiang, Yuehong Yang, Ziting Yao, Yinchun Chen, Yong Gao, Aihua Tan, Ming Liao, Johanna Schleutker, Jianfeng Xu, Yin
    Scientific Reports.2017;[Epub]     CrossRef
  • Regulation of theMEToncogene: molecular mechanisms
    Jack Zhang, Andy Babic
    Carcinogenesis.2016; 37(4): 345.     CrossRef
  • The RTK/ERK pathway is associated with prostate cancer risk on the SNP level: A pooled analysis of 41 sets of data from case–control studies
    Yang Chen, Tianyu Li, Xiaoqiang Yu, Jianfeng Xu, Jianling Li, Dexiang Luo, Zengnan Mo, Yanling Hu
    Gene.2014; 534(2): 286.     CrossRef
  • miR-210 over-expression enhances mesenchymal stem cell survival in an oxidative stress environment through antioxidation and c-Met pathway activation
    JianFeng Xu, ZheYong Huang, Li Lin, MingQiang Fu, YanHua Gao, YunLi Shen, YunZeng Zou, AiJun Sun, JuYing Qian, JunBo Ge
    Science China Life Sciences.2014; 57(10): 989.     CrossRef
  • Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2
    Mario Acunzo, Giulia Romano, Dario Palmieri, Alessandro Laganá, Michela Garofalo, Veronica Balatti, Alessandra Drusco, Mario Chiariello, Patrick Nana-Sinkam, Carlo M. Croce
    Proceedings of the National Academy of Sciences.2013; 110(21): 8573.     CrossRef
  • Gold nanoparticles trigger apoptosis and necrosis in lung cancer cells with low intracellular glutathione
    Min Liu, Xiaohu Gu, Ke Zhang, Yi Ding, Xinbing Wei, Xiumei Zhang, Yunxue Zhao
    Journal of Nanoparticle Research.2013;[Epub]     CrossRef
  • RTK/ERK Pathway under Natural Selection Associated with Prostate Cancer
    Yang Chen, Xianxiang Xin, Jie Li, Jianfeng Xu, Xiaoxiang Yu, Tianyu Li, Zengnan Mo, Yanling Hu, Antimo Migliaccio
    PLoS ONE.2013; 8(11): e78254.     CrossRef
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  • 71 Download
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Constitutive Expression of MAP Kinase Phosphatase-1 Confers Multi-drug Resistance in Human Glioblastoma Cells
Hana Yu, Junseong Park, Jungsul Lee, Kyungsun Choi, Chulhee Choi
Cancer Res Treat. 2012;44(3):195-201.   Published online September 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.3.195
AbstractAbstract PDFPubReaderePub
PURPOSE
Current treatment of glioblastoma after surgery consists of a combination of fractionated radiotherapy and temozolomide. However, it is difficult to completely remove glioblastoma because it has uncertain boundaries with surrounding tissues. Moreover, combination therapy is not always successful because glioblastoma has diverse resistances. To overcome these limitations, we examined the combined effects of chemotherapy and knockdown of mitogen-activated protein kinase phosphatase-1 (MKP-1).
MATERIALS AND METHODS
We used ten different anti-cancer drugs (cisplatin, cyclophosphoamide, doxorubicin, epirubicin, etoposide, 5-fluorouracil, gemcitabine, irinotecan, mitomycin C, and vincristine) to treat glioblastoma multiforme (GBM) cells. Knockdown of MKP-1 was performed using siRNA and lipofectamine. The basal level of MKP-1 in GBM was analyzed based on cDNA microarray data obtained from the Gene Expression Omnibus (GEO) databases.
RESULTS
Anti-cancer drug-induced cell death was significantly enhanced by knockdown of MKP-1, and this effect was most prominent in cells treated with irinotecan and etoposide. Treatment with these two drugs led to significantly increased phosphorylation of c-Jun N-terminal kinase (JNK) in a time-dependent manner, while pharmacological inhibition of JNK partially inhibited drug-induced cell death. Knockdown of MKP-1 also enhanced drug-induced phosphorylation of JNK.
CONCLUSION
Increased MKP-1 expression levels could be the cause of the high resistance to conventional chemotherapeutics in human GBM. Therefore, MKP-1 is an attractive target for overcoming drug resistance in this highly refractory malignancy.

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  • Platinum-based drugs in cancer treatment: Expanding horizons and overcoming resistance
    Mona Shahlaei, Shaahin Mohammadzadeh Asl, Atefe Derakhshani, Leonie Kurek, Johannes Karges, Robert Macgregor, Maryam Saeidifar, Irena Kostova, Ali Akbar Saboury
    Journal of Molecular Structure.2024; 1301: 137366.     CrossRef
  • Dual-specificity phosphatases: therapeutic targets in cancer therapy resistance
    Zahra Zandi, Bahareh Kashani, Zivar Alishahi, Atieh Pourbagheri-Sigaroodi, Fatemeh Esmaeili, Seyed H. Ghaffari, Davood Bashash, Majid Momeny
    Journal of Cancer Research and Clinical Oncology.2022; 148(1): 57.     CrossRef
  • Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas
    Jaewan Jeon, Sungmin Lee, Hyunwoo Kim, Hyunkoo Kang, HyeSook Youn, Sunmi Jo, BuHyun Youn, Hae Yu Kim
    International Journal of Molecular Sciences.2021; 22(10): 5111.     CrossRef
  • Time-dependent re-organization of biological processes by the analysis of the dynamic transcriptional response of yeast cells to doxorubicin
    Muhammed Erkan Karabekmez, Hilal Taymaz-Nikerel, Serpil Eraslan, Betul Kirdar
    Molecular Omics.2021; 17(4): 572.     CrossRef
  • MKP1 phosphatase is recruited by CXCL12 in glioblastoma cells and plays a role in DNA strand breaks repair
    Matthias Dedobbeleer, Estelle Willems, Jeremy Lambert, Arnaud Lombard, Marina Digregorio, Paul Noel Lumapat, Emmanuel Di Valentin, Stephen Freeman, Nicolas Goffart, Felix Scholtes, Bernard Rogister
    Carcinogenesis.2020; 41(4): 417.     CrossRef
  • RNA Interference Nanotherapeutics for Treatment of Glioblastoma Multiforme
    Prabhjeet Singh, Aditi Singh, Shruti Shah, Jalpa Vataliya, Anupama Mittal, Deepak Chitkara
    Molecular Pharmaceutics.2020; 17(11): 4040.     CrossRef
  • Dual-specificity MAP kinase phosphatases in health and disease
    Ole-Morten Seternes, Andrew M. Kidger, Stephen M. Keyse
    Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2019; 1866(1): 124.     CrossRef
  • Protein Phosphatases—A Touchy Enemy in the Battle Against Glioblastomas: A Review
    Arata Tomiyama, Tatsuya Kobayashi, Kentaro Mori, Koichi Ichimura
    Cancers.2019; 11(2): 241.     CrossRef
  • Tyrosyl-DNA Phosphodiesterase 1 and Topoisomerase I Activities as Predictive Indicators for Glioblastoma Susceptibility to Genotoxic Agents
    Wenjie Wang, Monica Rodriguez-Silva, Arlet M. Acanda de la Rocha, Aizik L. Wolf, Yanhao Lai, Yuan Liu, William C. Reinhold, Yves Pommier, Jeremy W. Chambers, Yuk-Ching Tse-Dinh
    Cancers.2019; 11(10): 1416.     CrossRef
  • Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells
    Hilal Taymaz-Nikerel, Muhammed Erkan Karabekmez, Serpil Eraslan, Betül Kırdar
    Scientific Reports.2018;[Epub]     CrossRef
  • Expression Profiling of the MAP Kinase Phosphatase Family Reveals a Role for DUSP1 in the Glioblastoma Stem Cell Niche
    Bradley N. Mills, George P. Albert, Marc W. Halterman
    Cancer Microenvironment.2017; 10(1-3): 57.     CrossRef
  • Phosphatases and solid tumors: focus on glioblastoma initiation, progression and recurrences
    Matthias Dedobbeleer, Estelle Willems, Stephen Freeman, Arnaud Lombard, Nicolas Goffart, Bernard Rogister
    Biochemical Journal.2017; 474(17): 2903.     CrossRef
  • RACK1 affects glioma cell growth and differentiation through the CNTN2-mediated RTK/Ras/MAPK pathway
    YU YAN, YUGANG JIANG
    International Journal of Molecular Medicine.2016; 37(1): 251.     CrossRef
  • Inactivated Tianjin strain, a novel genotype of Sendai virus, induces apoptosis in HeLa, NCI-H446 and Hep3B cells
    JUN CHEN, HAN HAN, BIN WANG, LIYING SHI
    Oncology Letters.2016; 12(1): 49.     CrossRef
  • The oncogenic receptor ErbB2 modulates gemcitabine and irinotecan/SN-38 chemoresistance of human pancreatic cancer cells via hCNT1 transporter and multidrug-resistance associated protein MRP-2
    Nicolas Skrypek, Romain Vasseur, Audrey Vincent, Bélinda Duchêne, Isabelle Van Seuningen, Nicolas Jonckheere
    Oncotarget.2015; 6(13): 10853.     CrossRef
  • Targeting DUSPs in glioblastomas – wielding a double‐edged sword?
    Sheila Prabhakar, Swapna Asuthkar, William Lee, Srinivasulu Chigurupati, Eleonora Zakharian, Andrew J. Tsung, Kiran Kumar Velpula
    Cell Biology International.2014; 38(2): 145.     CrossRef
  • Is Mda‐7/IL‐24 a Potential Target and Biomarker for Enhancing Drug Sensitivity in Human Glioma U87 Cell Line?
    Qin Wang, Yu Zhu, Ping Yang
    The Anatomical Record.2013; 296(8): 1154.     CrossRef
  • TGF-β1 and hypoxia-dependent expression of MKP-1 leads tumor resistance to death receptor-mediated cell death
    J Park, J Lee, W Kang, S Chang, E-C Shin, C Choi
    Cell Death & Disease.2013; 4(2): e521.     CrossRef
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  • 69 Download
  • 18 Crossref
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Up-regulation of the DR5 Expression by Proteasome Inhibitor MG132 Augments TRAIL-Induced Apoptosis in Soft Tissue Sarcoma Cell Lines
Hee-Jeong Cheong, Kyu Sang Lee, In Sook Woo, Jong-Ho Won, Jae Ho Byun
Cancer Res Treat. 2011;43(2):124-130.   Published online June 30, 2011
DOI: https://doi.org/10.4143/crt.2011.43.2.124
AbstractAbstract PDFPubReaderePub
PURPOSE
Current chemotherapeutics for treating locally advanced or metastatic soft tissue sarcomas (STS) are limited. Accordingly, the present in vitro study was conducted to evaluate the effects of treatment of STS cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) applied as a single agent or in combination with a proteasome inhibitor, MG132.
MATERIALS AND METHODS
Sensitivity to TRAIL and activity of TRAIL-induced apoptotic pathways were analyzed in four STS cell lines: HTB-82 (rhabdomyosarcoma), HT-1080 (fibrosarcoma), HTB-93 (synovial sarcoma), and HTB-94 (chondrosarcoma). Reduction of the dye dimethylthiazolyl 2,5 diphenyltetrazolium bromide (MTT) was used to evaluate cytotoxic activity; western blots were used to evaluate TRAIL-induced apoptosis.
RESULTS
TRAIL induced apoptosis in HTB-93 cells, but had little effect in HTB-82, HT-1080, or HTB-94 cells. Expression of TRAIL receptor-1 and -2 did not correlate with sensitivity to TRAIL. Co-incubation of cells with TRAIL and a proteasome inhibitor, MG132, augmented the apoptotic effect of TRAIL in both TRAIL-sensitive and TRAIL-resistant cells. This effect was due to up-regulation of TRAIL receptors and members of the pro-apoptotic BCL-2 family by MG132.
CONCLUSION
These data show that combining TRAIL with MG132 enhances apoptosis and overcomes TRAIL resistance. This restoration of TRAIL sensitivity occurs through an increase in the expression of death receptor 5 and of pro-apoptotic BCL-2 family members such as BAX.

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  • TRAIL-induced apoptosis and proteasomal activity – Mechanisms, signalling and interplay
    Chiara Boccellato, Markus Rehm
    Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2024; 1871(4): 119688.     CrossRef
  • Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies
    Edoardo Agosti, Marco Zeppieri, Sara Antonietti, Tamara Ius, Marco Maria Fontanella, Pier Paolo Panciani
    Journal of Personalized Medicine.2024; 14(3): 261.     CrossRef
  • Proteasome inhibitors as anticancer agents
    Giorgia Gazzaroli, Andrea Angeli, Arianna Giacomini, Roberto Ronca
    Expert Opinion on Therapeutic Patents.2023; 33(11): 775.     CrossRef
  • Combination therapy with c-met inhibitor and TRAIL enhances apoptosis in dedifferentiated liposarcoma patient-derived cells
    Eun Byeol Jo, Young Sang Lee, Hyunjoo Lee, Jae Berm Park, Hyojun Park, Yoon-La Choi, Doopyo Hong, Sung Joo Kim
    BMC Cancer.2019;[Epub]     CrossRef
  • Disulfide bond-disrupting agents activate the tumor necrosis family-related apoptosis-inducing ligand/death receptor 5 pathway
    Mengxiong Wang, Mary E. Law, Bradley J. Davis, Elham Yaaghubi, Amanda F. Ghilardi, Renan B. Ferreira, Chi-Wu Chiang, Olga A. Guryanova, Daniel Kopinke, Coy D. Heldermon, Ronald K. Castellano, Brian K. Law
    Cell Death Discovery.2019;[Epub]     CrossRef
  • The combination of TRAIL and MG-132 induces apoptosis in both TRAIL-sensitive and TRAIL-resistant human follicular lymphoma cells
    Jemal Adem, Mine Eray, Jonna Eeva, Ulla Nuutinen, Jukka Pelkonen
    Leukemia Research.2018; 66: 57.     CrossRef
  • Chondrosarcoma: An overview of clinical behavior, molecular mechanisms mediated drug resistance and potential therapeutic targets
    Elahe Nazeri, Mohammad Gouran Savadkoohi, Keivan Majidzadeh-A, Rezvan Esmaeili
    Critical Reviews in Oncology/Hematology.2018; 131: 102.     CrossRef
  • TNF-related apoptosis-inducing ligand (TRAIL) for bone sarcoma treatment: Pre-clinical and clinical data
    Zakareya Gamie, Konstantinos Kapriniotis, Dimitra Papanikolaou, Emma Haagensen, Ricardo Da Conceicao Ribeiro, Kenneth Dalgarno, Anja Krippner-Heidenreich, Craig Gerrand, Eleftherios Tsiridis, Kenneth Samora Rankin
    Cancer Letters.2017; 409: 66.     CrossRef
  • Activation of TRAIL‐DR5 pathway promotes sensorineural degeneration in the inner ear
    Shyan‐Yuan Kao, Vitor Y.R. Soares, Arthur G. Kristiansen, Konstantina M. Stankovic
    Aging Cell.2016; 15(2): 301.     CrossRef
  • Prognostic significance of FOXM1 expression and antitumor effect of FOXM1 inhibition in synovial sarcomas
    Akira Maekawa, Kenichi Kohashi, Masaaki Kuda, Kunio Iura, Takeaki Ishii, Makoto Endo, Tetsuya Nakatsura, Yukihide Iwamoto, Yoshinao Oda
    BMC Cancer.2016;[Epub]     CrossRef
  • The Importance of Being Dead: Cell Death Mechanisms Assessment in Anti-Sarcoma Therapy
    Santiago Rello-Varona, David Herrero-Martín, Laura Lagares-Tena, Roser López-Alemany, Núria Mulet-Margalef, Juan Huertas-Martínez, Silvia Garcia-Monclús, Xavier García del Muro, Cristina Muñoz-Pinedo, Oscar Martínez Tirado
    Frontiers in Oncology.2015;[Epub]     CrossRef
  • Development of a Novel Class of Mitochondrial Ubiquinol–Cytochrome c Reductase Binding Protein (UQCRB) Modulators as Promising Antiangiogenic Leads
    Hye Jin Jung, Misun Cho, Yonghyo Kim, Gyoonhee Han, Ho Jeong Kwon
    Journal of Medicinal Chemistry.2014; 57(19): 7990.     CrossRef
  • Mitochondrial UQCRB regulates VEGFR2 signaling in endothelial cells
    Hye Jin Jung, Yonghyo Kim, Junghwa Chang, Sang Won Kang, Jeong Hun Kim, Ho Jeong Kwon
    Journal of Molecular Medicine.2013; 91(9): 1117.     CrossRef
  • Cell Death Pathways as Therapeutic Targets in Rhabdomyosarcoma
    Simone Fulda
    Sarcoma.2012; 2012: 1.     CrossRef
  • 11,441 View
  • 71 Download
  • 14 Crossref
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Effects of Triterpenoid Glycosides from Fresh Ginseng Berry on SW480 Human Colorectal Cancer Cell Line
Jing-Tian Xie, Guang-Jian Du, Eryn McEntee, Han H. Aung, Hui He, Sangeeta R. Mehendale, Chong-Zhi Wang, Chun-Su Yuan
Cancer Res Treat. 2011;43(1):49-55.   Published online March 31, 2011
DOI: https://doi.org/10.4143/crt.2011.43.1.49
AbstractAbstract PDFPubReaderePub
PURPOSE
The pharmacological activities, notably the anticancer properties, of bioactive constituents fromfresh American ginseng berry have not yet been well studied. In this study, we investigated the antiproliferative effects of fresh American ginseng berry extract (AGBE) and its representative triterpenoid glycosides using the human colorectal cancer cell line SW480.
MATERIALS AND METHODS
Using high performance liquid chromatography (HPLC), the contents of 8 ginsenosides in AGBE were determined. The cell growth inhibitory effects of AGBE and three triterpenoid glycosides (ginsenosides Rb3, Re, and Rg3) were evaluated by proliferation assay and 3H-thymidine incorporation assay. Cell cycle and apoptotic effects were analyzed by using flow cytometry after staining with propidium iodide and annexin V.
RESULTS
HPLC analysis data showed that AGBE has a distinct ginsenoside profile. AGBE inhibited SW480 cell growth significantly in a time-dependent (24-96 hours) and concentration-dependent (0.1-1.0 mg/mL) manner. Ginsenosides Rb3, Re, and Rg3 also possess significant antiproliferative activities on SW480 cells. 3H-thymidine incorporation assay indicated that AGBE and ginsenosides Rb3, Re, and Rg3 might inhibit the transferring and duplication of DNA in SW480 cells. Flow cytometric assay data suggested that AGBE arrested SW480 cells in S and G2/M phases, and significantly induced cell apoptosis.
CONCLUSION
AGBE and ginsenosides Rb3, Re, and Rg3 possessed significant antiproliferative effects and induced changes of morphological appearance on SW480 cells. The mechanisms of the antiproliferation of AGBE and tested ginsenosides involved could be cell cycle arrest and induction of apoptosis.

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  • A systematic review of ginsenoside biosynthesis, spatiotemporal distribution, and response to biotic and abiotic factors in American ginseng
    Lixia Tian, Ranran Gao, Yuxiang Cai, Junxian Chen, Hongmei Dong, Shanshan Chen, Zaichang Yang, Yu Wang, Linfang Huang, Zhichao Xu
    Food & Function.2024; 15(5): 2343.     CrossRef
  • Ginsenoside Re Suppress the Proliferation and Migration of MCF-7 Human Breast Cancer Cells
    Jin-Nyoung Ho
    Journal of the Korean Society of Food Science and Nutrition.2024; 53(3): 233.     CrossRef
  • Comprehensive phytochemicals analysis and anti‐myocardial ischemia activity of total saponins of American ginseng berry
    Le Li, Yunhe Liu, Hui Yu, Zhuo Li, Hongqiang Lin, Fulin Wu, Luying Tan, Caixia Wang, Pingya Li, Jinping Liu
    Journal of Food Biochemistry.2022;[Epub]     CrossRef
  • Pharmacological Properties of Ginsenoside Re
    Xiao-Yan Gao, Guan-Cheng Liu, Jian-Xiu Zhang, Ling-He Wang, Chang Xu, Zi-An Yan, Ao Wang, Yi-Fei Su, Jung-Joon Lee, Guang-Chun Piao, Hai-Dan Yuan
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Therapeutic effects of ginseng and ginsenosides on colorectal cancer
    Linxian Zhao, Yueming Zhang, Yajuan Li, Chen Li, Kai Shi, Kai Zhang, Ning Liu
    Food & Function.2022; 13(12): 6450.     CrossRef
  • Comparative Analysis of Panax ginseng Berries from Seven Cultivars Using UPLC-QTOF/MS and NMR-Based Metabolic Profiling
    Dahye Yoon, Bo-Ram Choi, Young-Chang Kim, Seon Min Oh, Hyoung-Geun Kim, Jang-Uk Kim, Nam-In Baek, Suhkmann Kim, Dae Young Lee
    Biomolecules.2019; 9(9): 424.     CrossRef
  • Multiple Effects of Ginseng Berry Polysaccharides: Plasma Cholesterol Level Reduction and Enteric Neoplasm Prevention
    Jin-Yi Wan, Wei-Hua Huang, Wei Zheng, Chan Woong Park, Su Hwan Kim, Dae Bang Seo, Kwang-Soon Shin, Jinxiang Zeng, Haiqiang Yao, Clara Sava-Segal, Chong-Zhi Wang, Chun-Su Yuan
    The American Journal of Chinese Medicine.2017; 45(06): 1293.     CrossRef
  • Process Optimization of Ginseng Berry Extract Fermentation by Lactobacillus sp. Strain KYH isolated from Fermented Kimchi and Product Analysis
    Yoo-Jin Ha, Sun-Kyun Yoo, Mee Ree Kim
    Journal of the East Asian Society of Dietary Life.2016; 26(1): 88.     CrossRef
  • Anticancer Activities of Protopanaxadiol‐ and Protopanaxatriol‐Type Ginsenosides and Their Metabolites
    Xiao-Jia Chen, Xiao-Jing Zhang, Yan-Mei Shui, Jian-Bo Wan, Jian-Li Gao, Ki-Wan Oh
    Evidence-Based Complementary and Alternative Medicine.2016;[Epub]     CrossRef
  • Metabonomic Profiling Reveals Cancer Chemopreventive Effects of American Ginseng on Colon Carcinogenesis in ApcMin/+ Mice
    Guoxiang Xie, Chong-Zhi Wang, Chunhao Yu, Yunping Qiu, Xiao-Dong Wen, Chun-Feng Zhang, Chun-Su Yuan, Wei Jia
    Journal of Proteome Research.2015; 14(8): 3336.     CrossRef
  • Establishment of Optimal Fermentation Conditions for Steam-dried Ginseng Berry via Friendly Bacteria and Its Antioxidant Activities
    Seung Tae Kim, Hee Jung Kim, Su Kil Jang, Do Ik Lee, Seong Soo Joo
    Korean Journal of Food Science and Technology.2013; 45(1): 77.     CrossRef
  • Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells
    Trang Thi Mai, JeongYong Moon, YeonWoo Song, Pham Quoc Viet, Pham Van Phuc, Jung Min Lee, Tae-Hoo Yi, Moonjae Cho, Somi Kim Cho
    Cancer Letters.2012; 321(2): 144.     CrossRef
  • 11,953 View
  • 94 Download
  • 12 Crossref
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Apoptosis and Expression of AQP5 and TGF-β in the Irradiated Rat Submandibular Gland
Jin Hwa Choi, Hong-Gyun Wu, Kyeong Cheon Jung, Seung Hee Lee, Eun Kyung Kwon
Cancer Res Treat. 2009;41(3):145-154.   Published online September 28, 2009
DOI: https://doi.org/10.4143/crt.2009.41.3.145
AbstractAbstract PDFPubReaderePub
Purpose

To evaluate the effect of X-ray irradiation on apoptosis and change of expression of aquaporin 5 (AQP5) and transforming growth factor-β(TGF-β) in the rat submandibular gland (SMG).

Materials and Methods

SMGs of 120 male Sprague-Dawley rats were irradiated with a single X-ray dose (3, 10, 20, or 30 Gy). At the early and late post-irradiation phase, apoptosis was measured by the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method, and expression of AQP5 and TGF-β was determined by immunohistochemical staining.

Results

At the late post-irradiation phase, increased apoptosis was evident and marked decreases of expression of AQP5 expression by acinar cells and TGF-β expression by ductal cells were evident.

Conclusion

Apoptosis after X-ray irradiation develops relatively late in rat SMG. Irradiation reduces AQP5 and TGF-β expression in different SMG cell types.

Citations

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  • Proton FLASH Radiotherapy Ameliorates Radiation-induced Salivary Gland Dysfunction and Oral Mucositis and Increases Survival in a Mouse Model of Head and Neck Cancer
    Priyanka Chowdhury, Anastasia Velalopoulou, Ioannis I. Verginadis, George Morcos, Phoebe E. Loo, Michele M. Kim, Seyyedeh Azar Oliaei Motlagh, Khayrullo Shoniyozov, Eric S. Diffenderfer, Emilio A. Ocampo, Mary Putt, Charles-Antoine Assenmacher, Enrico Rad
    Molecular Cancer Therapeutics.2024; 23(6): 877.     CrossRef
  • A single dose of radiation elicits comparable acute salivary gland injury to fractionated radiation
    Amanda L. Johnson, Sonia S. Elder, John G. McKendrick, Lizi M. Hegarty, Ella Mercer, Elaine Emmerson
    Disease Models & Mechanisms.2024;[Epub]     CrossRef
  • Oxidative‐antioxidant imbalance in chronic sialadenitis of submandibular gland in human and rat
    Jingyang Liu, Pei Liu, Lili Wei, Wei Li, Bo Li, Yong Cheng
    Oral Diseases.2023; 29(3): 1005.     CrossRef
  • Noninvasive Monitoring of Radiation-Induced Salivary Gland Vascular Injury
    E.R. Bolookat, L.J. Rich, V.K. Vincent-Chong, C.R. DeJohn, M. Merzianu, P.A. Hershberger, A.K. Singh, M. Seshadri
    Journal of Dental Research.2023; 102(4): 412.     CrossRef
  • Insights into the Function of Aquaporins in Gastrointestinal Fluid Absorption and Secretion in Health and Disease
    Giuseppe Calamita, Christine Delporte
    Cells.2023; 12(17): 2170.     CrossRef
  • Evaluation of the Radioprotective Effect of Silver Nanoparticles on Irradiated Submandibular Gland of Adult Albino Rats. A Histological and Sialochemical Study
    Manal R. Abd El-Haleem, Mona G. Amer, Amira E. Fares, Amany Hany Mohamed Kamel
    BioNanoScience.2022; 12(1): 13.     CrossRef
  • Regeneration potential of bone marrow derived mesenchymal stem cells and platelet rich plasma (PRP) on irradiation-induced damage of submandibular salivary gland in albino rats
    NH Mohamed, S. Shawkat, MS Moussa, NEB Ahmed
    Tissue and Cell.2022; 76: 101780.     CrossRef
  • Short-term and bystander effects of radiation on murine submandibular glands
    Hitoshi Uchida, Matthew H. Ingalls, Eri O. Maruyama, Carl J. Johnston, Eric Hernady, Roberta C. Faustoferri, Catherine E. Ovitt
    Disease Models & Mechanisms.2022;[Epub]     CrossRef
  • Insight into Salivary Gland Aquaporins
    Claudia D’Agostino, Osama A. Elkashty, Clara Chivasso, Jason Perret, Simon D. Tran, Christine Delporte
    Cells.2020; 9(6): 1547.     CrossRef
  • Physiological role of aquaporin 5 in salivary glands
    Kazuo Hosoi
    Pflügers Archiv - European Journal of Physiology.2016; 468(4): 519.     CrossRef
  • Aquaporins in Salivary Glands: From Basic Research to Clinical Applications
    Christine Delporte, Angélic Bryla, Jason Perret
    International Journal of Molecular Sciences.2016; 17(2): 166.     CrossRef
  • Down-regulation of AQP4 Inhibits Proliferation, Migration and Invasion of Human Breast Cancer Cells
    Y.-B. Li, Sheng-Rong Sun, X.-H. Han
    Folia Biologica.2016; 62(3): 131.     CrossRef
  • Effect of Phenylephrine Pretreatment on the Expressions of Aquaporin 5 and c-Jun N-Terminal Kinase in Irradiated Submandibular Gland
    Lichi Han, Lei Wang, Fuyin Zhang, Ke Jian Liu, Bin Xiang
    Radiation Research.2015; 183(6): 693.     CrossRef
  • Aquaporins in salivary glands and pancreas
    Christine Delporte
    Biochimica et Biophysica Acta (BBA) - General Subjects.2014; 1840(5): 1524.     CrossRef
  • AQP5: A novel biomarker that predicts poor clinical outcome in colorectal cancer
    TAO SHAN, XIJUAN CUI, WEI LI, WANRUN LIN, YIMING LI
    Oncology Reports.2014; 32(4): 1564.     CrossRef
  • Underlying protective mechanism of α1-adrenoceptor activation against irradiation-induced damage in rat submandibular gland
    Bin Xiang, Xiu-xiu Li, Fu-yin Zhang
    Archives of Oral Biology.2013; 58(9): 1238.     CrossRef
  • 10,902 View
  • 69 Download
  • 16 Crossref
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Proapoptotic Ginsenosides Compound K and Rh2 Enhance Fas-induced Cell Death of Human Astrocytoma Cells Through Distinct Apoptotic Signaling Pathways
Kyungsun Choi, Chulhee Choi
Cancer Res Treat. 2009;41(1):36-44.   Published online March 31, 2009
DOI: https://doi.org/10.4143/crt.2009.41.1.36
AbstractAbstract PDFPubReaderePub
Purpose

Malignant astrocytomas are among the commonest primary brain tumors and they have a grave prognosis, and so there is an urgent need to develop effective treatment. In this study, we investigated the molecular mechanisms that are responsible for the anti-tumor effect of ginsenosides on human astrocytoma cells.

Materials and Methods

We tested 13 different ginsenosides for their anti-tumor effect on human malignant astrocytoma cells in conjunction with Fas stimulation. In addition, the cell signaling pathways were explored by using pharmacological inhibitors and performing immunoblot analysis. DCF-DA staining and antioxidant experiments were performed to investigate the role of reactive oxygen species as one of the apoptosis-inducing mechanisms.

Results

Among the 13 different ginsenoside metabolites, compound K and Rh2 induced apoptotic cell death of the astrocytoma cells in a caspase- and p38 MAPK-dependent manner, yet the same treatment had no cytotoxic effect on the primary cultured human astrocytes. Combined treatment with ginsenosides and Fas ligand showed a synergistic cytotoxic effect, which was mediated by the reduction of intracellular reactive oxygen species.

Conclusion

These results suggest that ginsenoside metabolites in combination with Fas ligand may provide a new strategy to treat malignant astrocytomas, which are tumors that are quite resistant to conventional anti-cancer treatment.

Citations

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  • Compound K: A systematic review of its anticancer properties and probable mechanisms
    Dao Ngoc Hien Tam, Nguyen Hai Nam, Nguyen The Ky Cuong, Dang The Hung, Dang Thi Soa, Ahmad Altom, Linh Tran, Heba Elhadad, Nguyen Tien Huy
    Fundamental & Clinical Pharmacology.2023; 37(4): 684.     CrossRef
  • Antioxidant Activity of Panax ginseng to Regulate ROS in Various Chronic Diseases
    Md Niaj Morshed, Jong Chan Ahn, Ramya Mathiyalagan, Esrat Jahan Rupa, Reshmi Akter, Md. Rezaul Karim, Dae Hyo Jung, Dong Uk Yang, Deok Chun Yang, Seok Kyu Jung
    Applied Sciences.2023; 13(5): 2893.     CrossRef
  • Anticancer therapeutic effect of ginsenosides through mediating reactive oxygen species
    Xiaonan Li, Donghui Cao, Siming Sun, Yuehui Wang
    Frontiers in Pharmacology.2023;[Epub]     CrossRef
  • Metabolites-Based Network Pharmacology to Preliminarily Verify In Vitro Anti-Inflammatory Effect of Ardisiacrispin B
    Wen Zhou, Guixiang Yang, Yushuang Wen, Qian Xiao, Le Sun, Yongjun Li, Zipeng Gong, Yonglin Wang
    International Journal of Molecular Sciences.2023; 24(23): 17059.     CrossRef
  • The promising therapeutic potentials of ginsenosides mediated through p38 MAPK signaling inhibition
    El-Shaimaa A. Arafa, Mohamed S. Refaey, Omnia A.M. Abd El-Ghafar, Emad H.M. Hassanein, Ahmed M. Sayed
    Heliyon.2021; 7(11): e08354.     CrossRef
  • Ginseng: A dietary supplement as immune-modulator in various diseases
    Muhammad Riaz, Najm Ur Rahman, Muhammad Zia-Ul-Haq, Hawa Z.E. Jaffar, Rosana Manea
    Trends in Food Science & Technology.2019; 83: 12.     CrossRef
  • Apoptotic Pathway as the Therapeutic Target for Anticancer Traditional Chinese Medicines
    Weixiao An, Honglin Lai, Yangyang Zhang, Minghua Liu, Xiukun Lin, Shousong Cao
    Frontiers in Pharmacology.2019;[Epub]     CrossRef
  • Protective effect of ginsenoside metabolite compound K against diabetic nephropathy by inhibiting NLRP3 inflammasome activation and NF-κB/p38 signaling pathway in high-fat diet/streptozotocin-induced diabetic mice
    Wu Song, Lin Wei, Yanwei Du, Yimei Wang, Shuang Jiang
    International Immunopharmacology.2018; 63: 227.     CrossRef
  • Functional role of ginseng-derived compounds in cancer
    Akash Ahuja, Ji Hye Kim, Jong-Hoon Kim, Young-Su Yi, Jae Youl Cho
    Journal of Ginseng Research.2018; 42(3): 248.     CrossRef
  • Synthesis and Characterization of the Hemi‐Salen Ligands and Their Triboron Complexes: Spectroscopy and Examination of Anticancer Properties
    Ahmet Kilic, Ismail Koyuncu, Mustafa Durgun, Ismail Ozaslan, İbrahim Halil Kaya, Ataman Gönel
    Chemistry & Biodiversity.2018;[Epub]     CrossRef
  • Role of ginsenosides in reactive oxygen species-mediated anticancer therapy
    Islam M.D. Sodrul, Chenying Wang, Xiangfeng Chen, Jing Du, Hongxiang Sun
    Oncotarget.2018; 9(2): 2931.     CrossRef
  • Anticancer effect of joboksansam, Korean wild ginseng germinated from bird feces
    Jae Gwang Park, Wie-Soo Kang, Kyung Tae Park, Dong Jun Park, Adithan Aravinthan, Jong-Hoon Kim, Jae Youl Cho
    Journal of Ginseng Research.2016; 40(3): 304.     CrossRef
  • Korean Red Ginseng water extract arrests growth of xenografted lymphoma cells
    Jae Gwang Park, Young-Jin Son, Adithan Aravinthan, Jong-Hoon Kim, Jae Youl Cho
    Journal of Ginseng Research.2016; 40(4): 431.     CrossRef
  • Isolation and identification of antiproliferative substances from ginseng fermented using Ganoderma lucidum mycelia
    Gwi Yeong Jang, Eun Mi Joung, Sang Hoon Lee, Jae-Hyun Jeong, Bang Yeon Hwang, Jin Tae Hong, Junsoo Lee, Heon Sang Jeong
    Food Science and Biotechnology.2015; 24(2): 567.     CrossRef
  • Ginsenoside compound K induces apoptosis in nasopharyngeal carcinoma cells via activation of apoptosis-inducing factor
    Carmen Ka-Man Law, Hoi-Hin Kwok, Po-Ying Poon, Chi-Chiu Lau, Zhi-Hong Jiang, William Chi-Shing Tai, Wendy Wen-Luan Hsiao, Nai-Ki Mak, Patrick Ying-Kit Yue, Ricky Ngok-Shun Wong
    Chinese Medicine.2014;[Epub]     CrossRef
  • Effects of compound K on hyperglycemia and insulin resistance in rats with type 2 diabetes mellitus
    Shuang Jiang, Dayong Ren, Jianrui Li, Guangxin Yuan, Hongyu Li, Guangyu Xu, Xiao Han, Peige Du, Liping An
    Fitoterapia.2014; 95: 58.     CrossRef
  • 20‐O‐β‐d‐Glucopyranosyl‐20(S)‐Protopanaxadiol Suppresses UV‐Induced MMP‐1 Expression Through AMPK‐Mediated mTOR Inhibition as a Downstream of the PKA‐LKB1 Pathway
    Dong Joo Shin, Jong‐Eun Kim, Tae‐Gyu Lim, Eun Hee Jeong, Gaeun Park, Nam Joo Kang, Jun‐Seong Park, Myeong‐Hun Yeom, Deok Kun Oh, Ann M. Bode, Zigang Dong, Hyong Joo Lee, Ki Won Lee
    Journal of Cellular Biochemistry.2014; 115(10): 1702.     CrossRef
  • Compound K Induces Apoptosis of Bladder Cancer T24 Cells Via Reactive Oxygen Species-Mediated p38 MAPK Pathway
    Han Wang, Dandan Jiang, Jing Liu, Shuhong Ye, Shan Xiao, Wenwen Wang, Zhongyan Sun, Yuping Xie, Jihui Wang
    Cancer Biotherapy and Radiopharmaceuticals.2013; 28(8): 607.     CrossRef
  • 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol, a metabolite of ginseng, inhibits colon cancer growth by targeting TRPC channel-mediated calcium influx
    Jeong Ah Hwang, Mun Kyung Hwang, Yongwoo Jang, Eun Jung Lee, Jong-Eun Kim, Mi Hyun Oh, Dong Joo Shin, Semi Lim, Geun og Ji, Uhtaek Oh, Ann M. Bode, Zigang Dong, Ki Won Lee, Hyong Joo Lee
    The Journal of Nutritional Biochemistry.2013; 24(6): 1096.     CrossRef
  • Recent Methodology in Ginseng Analysis
    Seung-Hoon Baek, Ok-Nam Bae, Jeong-Hill Park
    Journal of Ginseng Research.2012; 36(2): 119.     CrossRef
  • Identification and Characterization of the Rhizobium sp. Strain GIN611 Glycoside Oxidoreductase Resulting in the Deglycosylation of Ginsenosides
    Eun-Mi Kim, Juhan Kim, Joo-Hyun Seo, Jun-Seong Park, Duck-Hee Kim, Byung-Gee Kim
    Applied and Environmental Microbiology.2012; 78(1): 242.     CrossRef
  • Compound K, a metabolite of ginsenosides, induces cardiac protection mediated nitric oxide via Akt/PI3K pathway
    Yasuo M. Tsutsumi, Rie Tsutsumi, Kazuaki Mawatari, Yutaka Nakaya, Michiko Kinoshita, Katsuya Tanaka, Shuzo Oshita
    Life Sciences.2011; 88(15-16): 725.     CrossRef
  • Synthesis of 20S-protopanaxadiol β-D-galactopyranosides
    L. N. Atopkina, V. A. Denisenko
    Chemistry of Natural Compounds.2011; 47(1): 79.     CrossRef
  • TRAIL promotes caspase-dependent pro-inflammatory responses via PKCδ activation by vascular smooth muscle cells
    S Song, K Choi, S-W Ryu, S W Kang, C Choi
    Cell Death & Disease.2011; 2(11): e223.     CrossRef
  • Compound K, a Metabolite of Ginseng Saponin, Induces Mitochondria-Dependent and Caspase-Dependent Apoptosis via the Generation of Reactive Oxygen Species in Human Colon Cancer Cells
    In Kyung Lee, Kyoung Ah Kang, Chae Moon Lim, Ki Cheon Kim, Hee Sun Kim, Dong Hyun Kim, Bum Joon Kim, Weon Young Chang, Jae Hyuck Choi, Jin Won Hyun
    International Journal of Molecular Sciences.2010; 11(12): 4916.     CrossRef
  • Ginseng saponin metabolite induces apoptosis in MCF-7 breast cancer cells through the modulation of AMP-activated protein kinase
    Areum Daseul Kim, Kyoung Ah Kang, Rui Zhang, Chae Moon Lim, Hee Sun Kim, Dong Hyun Kim, You Jin Jeon, Chang Hyun Lee, Jinny Park, Weon Young Chang, Jin Won Hyun
    Environmental Toxicology and Pharmacology.2010; 30(2): 134.     CrossRef
  • Compound K Inhibits Basic Fibroblast Growth Factor-Induced Angiogenesis via Regulation of p38 Mitogen Activated Protein Kinaseand AKT in Human Umbilical Vein Endothelial Cells
    Arong Jeong, Hyo-Jung Lee, Soo-Jin Jeong, Hyo-Jeong Lee, Eun-Ok Lee, Hyunsu Bae, Sung-Hoon Kim
    Biological and Pharmaceutical Bulletin.2010; 33(6): 945.     CrossRef
  • Caspase-dependent generation of reactive oxygen species in human astrocytoma cells contributes to resistance to TRAIL-mediated apoptosis
    K Choi, S-W Ryu, S Song, H Choi, S W Kang, C Choi
    Cell Death & Differentiation.2010; 17(5): 833.     CrossRef
  • Intestinal Metabolite Compound K of Ginseng Saponin Potently Attenuates Metastatic Growth of Hepatocellular Carcinoma by Augmenting Apoptosis via a Bid-Mediated Mitochondrial Pathway
    Gang Song, Shiguang Guo, Weiwei Wang, Chun Hu, Yubing Mao, Bing Zhang, Hong Zhang, Tianhui Hu
    Journal of Agricultural and Food Chemistry.2010; 58(24): 12753.     CrossRef
  • Aqueous extract of the medicinal plant Patrinia villosa Juss. Induces angiogenesis via activation of focal adhesion kinase
    Jongwook Jeon, Jungwhoi Lee, Chaehyun Kim, Yuri An, Chulhee Choi
    Microvascular Research.2010; 80(3): 303.     CrossRef
  • 12,588 View
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Analysis of Cellular Changes Resulting from Forced Expression of Dickkopf-1 in Hepatocellular Carcinoma Cells
Mi Hee Kwack, Sun Young Hwang, In Seok Jang, Sang Uk Im, Jin Oh Kim, Moon Kyu Kim, Jung Chul Kim, Young Kwan Sung
Cancer Res Treat. 2007;39(1):30-36.   Published online March 31, 2007
DOI: https://doi.org/10.4143/crt.2007.39.1.30
AbstractAbstract PDFPubReaderePub
Purpose

Recent studies have shown that Dickkopf-1 (DKK-1) is overexpressed in some tumors, including hepatocellular carcinoma. However, the role of increased DKK-1 in these tumors is not known. In this study, the DKK-1 expression in hepatocellular carcinoma (HCC) cell lines was evaluated and the effect of DKK-1 overexpression in HCC cell lines was studied.

Materials and Methods

The expression of DKK-1 in hepatocellular carcinoma cell lines was evaluated by RT-PCR. Stable cell lines that overexpressed DKK-1 were established. Cell growth, adhesion, migration and invasion assays were performed.

Results

RT-PCR analysis showed that 5 out of 8 HCC cell lines expressed DKK-1. The forced expression of DKK-1 suppressed the growth of cells and increased the population of cells in the sub-G1 phase. In addition, DKK-1 reduced the cellular adhesion capacity to collagen type I and fibronectin, and it increased migratory capacity. However, overexpression of DKK-1 did not increase the invasion capacity of the HCC cell line.

Conclusion

Collectively, our data suggest that overexpression of DKK-1 affects the biology of HCC cells.

Citations

Citations to this article as recorded by  
  • Non-invasive biomarkers for the detection of hepatocellular carcinoma
    Daniela Campion, Alessandra Tucci, Paola Ponzo, Gian Paolo Caviglia
    Minerva Biotecnologica.2019;[Epub]     CrossRef
  • DKK1 promotes hepatocellular carcinoma inflammation, migration and invasion: Implication of TGF-β1
    Maha Fezza, Mayssam Moussa, Rita Aoun, Rita Haber, George Hilal, Masaru Katoh
    PLOS ONE.2019; 14(9): e0223252.     CrossRef
  • MicroRNA-320a downregulation mediates human liver cancer cell proliferation through the Wnt/β-catenin signaling pathway
    Caicheng Lu, Zengwei Liao, Minxian Cai, Guirong Zhang
    Oncology Letters.2017; 13(2): 573.     CrossRef
  • Musashi1 regulates survival of hepatoma cell lines by activation of Wnt signalling pathway
    Kunlun Chen, Qing Gao, Wei Zhang, Zhongwei Liu, Jiangyi Cai, Ying Liu, Jinkai Xu, Jie Li, Yi Yang, Xin Xu
    Liver International.2015; 35(3): 986.     CrossRef
  • Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma
    Seung Up Kim, Jeon Han Park, Hyon-Suk Kim, Jae Myun Lee, Hyun Gyu Lee, Hyemi Kim, Sung Hoon Choi, Shinhwa Baek, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Jong Doo Lee, Kwang-Hyub Han
    Yonsei Medical Journal.2015; 56(5): 1296.     CrossRef
  • Serum level of DKK-1 and its prognostic potential in non–small cell lung cancer
    Liang-liang Dong, Lu-yun Qu, Li-yan Chu, Xiao-hui Zhang, Ying-hui Liu
    Diagnostic Pathology.2014;[Epub]     CrossRef
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Cell Cycle Regulatory Protein Expression Profiles by Adenovirus p53 Infection in Human Papilloma Virus-associated Cervical Cancer Cells
Yong-Seok Lee, Su-Mi Bae, Sun-Young Kwak, Dong-Chun Park, Yong-Wook Kim, Soo-Young Hur, Eun-Kyung Park, Byoung-Don Han, Young-Joo Lee, Chong-Kook Kim, Do Kang Kim, Woong-Shick Ahn
Cancer Res Treat. 2006;38(3):168-177.   Published online June 30, 2006
DOI: https://doi.org/10.4143/crt.2006.38.3.168
AbstractAbstract PDFPubReaderePub
Purpose

The tumor suppressor gene, p53, has been established as an essential component for the suppression of tumor cell growth. In this study, we investigated the time-course anticancer effects of adenoviral p53 (Adp53) infection on human ovarian cancer cells to provide insight into the molecular-level understanding of the growth suppression mechanisms involved in Adp53-mediated apoptosis and cell cycle arrest.

Materials and Methods

Three human cervical cancer cell lines (SiHa, CaSki, HeLa and HT3) were used. The effect of Adp53 infection was studied via cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay.

Results

Adp53 exerts a significant role in suppressing cervical cancer cell growth. Adp53 also showed growth inhibitory effects in each cell line, and it induced apoptosis and cell cycle arrest. Adp53 differentially regulated the expression of genes and proteins, and the gene expression profiles in the SiHa cells revealed that the p21, p53 and mdm2 expres sions were significantly up-regulated at 24 and 48 hr. Western blot shows that the p21 and p53 expression-levels were significantly increased after Adp53 infection. In addition, in all cell lines, both the CDK4 and PCNA protein expression levels were decreased 48 h after Adp53 infection. Cell cycle arrest at the G1 phase was induced only in the SiHa and HeLa cells, suggesting that exogenous infection of Adp53 in cancer cells was significantly different from the other HPV-associated cervical cancer cells.

Conclusion

Adp53 can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest, as well as through the regulation of the cell cycle-related proteins. The Adp53-mediated apoptosis can be employed as an advanced strategy for developing preferential tumor cell-specific delivery.

Citations

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  • Health‐promoting bioactivity and in vivo genotoxicity evaluation of a hemiepiphyte fig, Ficus dubia
    Uthaiwan Suttisansanee, Pornsiri Pitchakarn, Pisamai Ting, Woorawee Inthachat, Parunya Thiyajai, Daraphan Rodthayoy, Jirarat Karinchai, Bhanumas Chantarasuwan, Onanong Nuchuchua, Piya Temviriyanukul
    Food Science & Nutrition.2021; 9(4): 2269.     CrossRef
  • Comprehensive Data of P53 R282 Gene Mutation with Human Papillomaviruses (HPV)-Associated Oral Squamous Cell Carcinoma (OSCC)
    Tipaya Ekalaksananan, Weerayut Wongjampa, Pensiri Phusingha, Jureeporn Chuerduangphui, Patravoot Vatanasapt, Supannee Promthet, Natcha Patarapadungkit, Chamsai Pientong
    Pathology & Oncology Research.2020; 26(2): 1191.     CrossRef
  • Etoposide radiosensitizes p53-defective cholangiocarcinoma cell lines independent of their G2 checkpoint efficacies
    Arunee Hematulin, Sutiwan Meethang, Kitsana Utapom, Sopit Wongkham, Daniel Sagan
    Oncology Letters.2018;[Epub]     CrossRef
  • Effect and Safety of Recombinant Adenovirus-p53 Transfer Combined with Radiotherapy on Long-Term Survival of Locally Advanced Cervical Cancer
    Xing Su, Wen-juan Chen, Shao-wen Xiao, Xiao-fan Li, Gang Xu, Jian-ji Pan, Shan-wen Zhang
    Human Gene Therapy.2016; 27(12): 1008.     CrossRef
  • Celecoxib, a COX-2 Selective Inhibitor, Induces Cell Cycle Arrest at the G2/M Phase in HeLa Cervical Cancer Cells
    Agustina Setiawati
    Asian Pacific Journal of Cancer Prevention.2016; 17(4): 1655.     CrossRef
  • Cisplatin sensitivity and mechanisms of anti-HPV16 E6-ribozyme on cervical carcinoma CaSKi cell line
    Zhiguo Rao, Jianfei Gao, Bicheng Zhang, Bo Yang, Jiren Zhang
    The Chinese-German Journal of Clinical Oncology.2012; 11(4): 237.     CrossRef
  • 16,918 View
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Augmentation of Sodium Butyrate-induced Apoptosis by Phosphatidylinositol 3-kinase Inhibition in the Human Cervical Cancer Cell-line
Jung Kyu Park, Chi Heum Cho, Sabarish Ramachandran, So Jin Shin, Sang Hoon Kwon, Sun Young Kwon, Soon Do Cha
Cancer Res Treat. 2006;38(2):112-117.   Published online April 30, 2006
DOI: https://doi.org/10.4143/crt.2006.38.2.112
AbstractAbstract PDFPubReaderePub
Purpose

Sodium butyrate (NaBT) is principally a histone deacetylase (HDAC) inhibitor, and it has the potential to arrest HPV-positive carcinoma cells at the G1 to S phase transition of the cell cycle. The aim of study was to determine whether phosphatidylinositol 3-kinase (PI3K) inhibition can enhance the inhibitory effect of NaBT on a human cervical cancer cell line (HeLa).

Materials and Methods

Cervical cancer cells (HeLa) were treated with NaBT alone or in combination with the PI3K inhibitors wortmannin or LY294002. Cell viability analysis and FACS analysis were carried out. The expressions of the cell cycle related proteins were evaluated by Western-blot analysis.

Results

Inhibition of PI3K enhanced NaBT-mediated apoptosis and this decreased the HeLa cell viability. Either wortmannin or LY294002, combined with NaBT, enhanced the activation of caspase 3 and caspase 9, and this enhanced the subsequent cleavage of poly (ADP-ribose) polymerase (PARP). Cervical cancer cells were arrested in the subG1 and G2/M phase, as was detected by FACS analysis. NaBT treatment in combination with PI3K inhibitors showed the increased expression of the CDK inhibitors p21Cip1/Waf1 and p27Kip1, in a p53 dependent manner, and also the increased dephosphorylation of Rb whereas there was a reduction in the expression levels of cyclin A, cyclin D1 and cyclin B1.

Conclusion

The results demonstrate that inhibition of PI3K enhances NaBT-mediated cervical cancer cell apoptosis through the activation of the caspase pathway. Moreover, these findings will support future investigation using the PI3K inhibitors in combination with adjuvant treatment for treating carcinoma of the cervix.

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  • Targeting Cervical Cancer Stem Cells by Phytochemicals
    Tanya Tripathi, Joni Yadav, Divya Janjua, Apoorva Chaudhary, Udit Joshi, Anna Senrung, Arun Chhokar, Nikita Aggarwal, Alok Chandra Bharti
    Current Medicinal Chemistry.2024; 31(32): 5222.     CrossRef
  • Human papillomavirus molecular prevalence in south China and the impact on vaginal microbiome of unvaccinated women
    Tingting Wang, Weili Li, Mingya Cai, Shushen Ji, Yufang Wang, Nan Huang, Yancheng Jiang, Zhishan Zhang, Jack A. Gilbert
    mSystems.2024;[Epub]     CrossRef
  • Butyrate as a Potential Modulator in Gynecological Disease Progression
    Nayeon Kim, Changwon Yang
    Nutrients.2024; 16(23): 4196.     CrossRef
  • The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy
    Iason Psilopatis, Nikolaos Garmpis, Anna Garmpi, Kleio Vrettou, Panagiotis Sarantis, Evangelos Koustas, Efstathios A. Antoniou, Dimitrios Dimitroulis, Gregory Kouraklis, Michail V. Karamouzis, Georgios Marinos, Konstantinos Kontzoglou, Afroditi Nonni, Kon
    Cancers.2023; 15(8): 2222.     CrossRef
  • Histone Deacetylase Inhibitors as Therapeutic Interventions on Cervical Cancer Induced by Human Papillomavirus
    Natália Lourenço de Freitas, Maria Gabriela Deberaldini, Diana Gomes, Aline Renata Pavan, Ângela Sousa, Jean Leandro Dos Santos, Christiane P. Soares
    Frontiers in Cell and Developmental Biology.2021;[Epub]     CrossRef
  • Guanine nucleotide binding protein like-1 (GNL1) promotes cancer cell proliferation and survival through AKT/p21 CIP1 signaling cascade
    Rehna Krishnan, Mariappan Murugiah, Naga Padma Lakshmi,, Sundarasamy Mahalingam, Carl-Henrik Heldin
    Molecular Biology of the Cell.2020; 31(26): 2904.     CrossRef
  • Cellular Effects of Butyrate on Vascular Smooth Muscle Cells are Mediated through Disparate Actions on Dual Targets, Histone Deacetylase (HDAC) Activity and PI3K/Akt Signaling Network
    Omana P. Mathew, Kasturi Ranganna, Joseph Mathew, Meiling Zhu, Zivar Yousefipour, Chelliah Selvam, Shirlette G. Milton
    International Journal of Molecular Sciences.2019; 20(12): 2902.     CrossRef
  • The Potential Value of the PI3K/Akt/mTOR Signaling Pathway for Assessing Prognosis in Cervical Cancer and as a Target for Therapy
    Afsane Bahrami, Malihe Hasanzadeh, Seyed Mahdi Hassanian, Soodabeh ShahidSales, Majid Ghayour‐Mobarhan, Gordon A. Ferns, Amir Avan
    Journal of Cellular Biochemistry.2017; 118(12): 4163.     CrossRef
  • The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p21-dependent pathways
    Igor Hrgovic, Monika Doll, Johannes Kleemann, Xiao-Fan Wang, Nadja Zoeller, Andreas Pinter, Stefan Kippenberger, Roland Kaufmann, Markus Meissner
    BMC Cancer.2016;[Epub]     CrossRef
  • The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses
    Lifang Zhang, Jianhong Wu, Ming Tat Ling, Liang Zhao, Kong-Nan Zhao
    Molecular Cancer.2015;[Epub]     CrossRef
  • Wortmannin potentiates the combined effect of etoposide and cisplatin in human glioma cells
    Elzbieta Pastwa, Tomasz Poplawski, Urszula Lewandowska, Stella B. Somiari, Janusz Blasiak, Richard I. Somiari
    The International Journal of Biochemistry & Cell Biology.2014; 53: 423.     CrossRef
  • The Role of Signaling Pathways in Cervical Cancer and Molecular Therapeutic Targets
    Joaquín Manzo-Merino, Adriana Contreras-Paredes, Elenaé Vázquez-Ulloa, Leticia Rocha-Zavaleta, Alma M. Fuentes-Gonzalez, Marcela Lizano
    Archives of Medical Research.2014; 45(7): 525.     CrossRef
  • A novel HDAC inhibitor OBP-801 and a PI3K inhibitor LY294002 synergistically induce apoptosis via the suppression of survivin and XIAP in renal cell carcinoma
    TAKESHI YAMADA, MANO HORINAKA, MASAHIDE SHINNOH, TAKASHI YOSHIOKA, TSUNEHARU MIKI, TOSHIYUKI SAKAI
    International Journal of Oncology.2013; 43(4): 1080.     CrossRef
  • Cytoplasmic translocation of p21 mediates NUPR1‐induced chemoresistance
    Andrew J. Vincent, Suping Ren, Lillianne G. Harris, Daniel J. Devine, Rajeev S. Samant, Oystein Fodstad, Lalita A. Shevde
    FEBS Letters.2012; 586(19): 3429.     CrossRef
  • Effect of butyrate on aromatase cytochrome P450 levels in HT29, DLD-1 and LoVo colon cancer cells
    Agnieszka Anna Rawłuszko, Sylwia Sławek, Armin Gollogly, Katarzyna Szkudelska, Paweł Piotr Jagodziński
    Biomedicine & Pharmacotherapy.2012; 66(2): 77.     CrossRef
  • Targeting Interleukin-4 Receptor α with Hybrid Peptide for Effective Cancer Therapy
    Liying Yang, Tomohisa Horibe, Masayuki Kohno, Mari Haramoto, Koji Ohara, Raj K. Puri, Koji Kawakami
    Molecular Cancer Therapeutics.2012; 11(1): 235.     CrossRef
  • Butyrate Induces Expression of 17β-Hydroxysteroid Dehydrogenase Type 1 in HT29 and SW707 Colorectal Cancer Cells
    Agnieszka Anna Rawłuszko, Piotr Krokowicz, Paweł Piotr Jagodziński
    DNA and Cell Biology.2011; 30(9): 661.     CrossRef
  • Butyrate increases the formation of anti-angiogenic vascular endothelial growth factor variants in human lung microvascular endothelial cells
    J. Ciura, P. P. Jagodziński
    Molecular Biology Reports.2010; 37(8): 3729.     CrossRef
  • Bean (Phaseolus vulgaris L.) polysaccharides modulate gene expression in human colon cancer cells (HT-29)
    R. Campos-Vega, R.G. Guevara-Gonzalez, B.L. Guevara-Olvera, B. Dave Oomah, G. Loarca-Piña
    Food Research International.2010; 43(4): 1057.     CrossRef
  • N-Hydroxy-7-(2-naphthylthio) Heptanomide Inhibits Retinal and Choroidal Angiogenesis
    Jeong Hun Kim, Jin Hyoung Kim, Meeyeon Oh, Young Suk Yu, Kyu-Won Kim, Ho Jeong Kwon
    Molecular Pharmaceutics.2009; 6(2): 513.     CrossRef
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  • 59 Download
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Arsenic Trioxide Induces Apoptosis in Human Colorectal Adenocarcinoma HT-29 Cells Through ROS
Young Cha, Dae-Weon Park, Chu Hee Lee, Suk-Hwan Baek, Seong-Yong Kim, Jae-Ryong Kim, Jung Hye Kim
Cancer Res Treat. 2006;38(1):54-60.   Published online February 28, 2006
DOI: https://doi.org/10.4143/crt.2006.38.1.54
AbstractAbstract PDFPubReaderePub
Purpose

Treatment with arsenic trioxide (As2O3) results in a wide range of cellular effects that includes induction of apoptosis, inhibition of cell growth, promotion or inhibition of cellular differentiation, and inhibition of angiogenesis through a variety of mechanisms. The mechanisms of As2O3-induced cell death have been mainly studied in hematological cancers, and those mechanisms in solid cancers have yet to be clearly defined. In this study, the mechanisms by which As2O3 induces apoptosis in human colorectal adenocarcinoma HT-29 cells were investigated.

Materials and Methods

To examine the levels of apoptosis, HT-29 cells were treated with As2O3 and then we measured the percentage of Annexin V binding cells, the amount of ROS production and the mitochondrial membrane potential. Western blot analysis was performed to identify the activated caspases after As2O3 exposure, and we compared the possible target molecules of apoptosis. As2O3 treatment induced the loss of the mitochondrial membrane potential and an increase of ROS, as well as activation of caspase-3, -7, -9 and -10.

Results

As2O3 induced apoptosis via the production of reactive oxygen species and the loss of the mitochondrial membrane potential. As2O3 induced the activation of caspase-3, -7, -9 and -10. Furthermore, As2O3 treatment downregulates the Mcl-1 and Bcl-2 expressions, and the release of cytochrome c and an apoptosis-inducing factor (AIF). Pretreating the HT-29 cells with N-acetyl-L-cysteine, which is a thiol-containing antioxidant, inhibited the As2O3-induced apoptosis and caspase activation.

Conclusion

Taken together, these results suggest that the generation of reactive oxygen species (ROS) by As2O3 might play an important role in the regulation of As2O3-induced apoptosis. This cytotoxicity is mediated through a mitochondria-dependent apoptotic signal pathway in HT-29 cells.

Citations

Citations to this article as recorded by  
  • Arsenic trioxide: applications, mechanisms of action, toxicity and rescue strategies to date
    Meng Yan, Hao Wang, Rui Wei, Wenwen Li
    Archives of Pharmacal Research.2024; 47(3): 249.     CrossRef
  • Inorganic arsenic exposure promotes malignant progression by HDAC6‐mediated down‐regulation of HTRA1
    Jiafeng Chen, Cece Lei, Daibang Nie, Huan Ge, Jian Li, Changbin Lei, Wang Wang
    Journal of Applied Toxicology.2023; 43(8): 1214.     CrossRef
  • Olaparib synergizes with arsenic trioxide by promoting apoptosis and ferroptosis in platinum-resistant ovarian cancer
    Sangsang Tang, Yuanming Shen, Xinyi Wei, Zhangjin Shen, Weiguo Lu, Junfen Xu
    Cell Death & Disease.2022;[Epub]     CrossRef
  • Combination of Arsenic Trioxide and Valproic Acid Efficiently Inhibits Growth of Lung Cancer Cells via G2/M-Phase Arrest and Apoptotic Cell Death
    Hyun Kyung Park, Bo Ram Han, Woo Hyun Park
    International Journal of Molecular Sciences.2020; 21(7): 2649.     CrossRef
  • Arsenic trioxide induces growth inhibition and death in human pulmonary artery smooth muscle cells accompanied by mitochondrial increase and GSH depletion
    Woo Hyun Park, Bo Ran Han, Hyun Kyung Park, Sung Zoo Kim
    Environmental Toxicology.2018; 33(8): 833.     CrossRef
  • PI3K/Akt/mTOR Signaling Pathway and the Biphasic Effect of Arsenic in Carcinogenesis
    Qiao Yi Chen, Max Costa
    Molecular Pharmacology.2018; 94(1): 784.     CrossRef
  • Anticytotoxic and Radical Scavenging Activities of Acer tegmentosum Maxim Stem Extracts
    Tae-Jin Rhim
    Journal of Environmental Science International.2015; 24(11): 1315.     CrossRef
  • Calpain and Reactive Oxygen Species Targets Bax for Mitochondrial Permeabilisation and Caspase Activation in Zerumbone Induced Apoptosis
    Praveen K. Sobhan, Mahendra Seervi, Lokesh Deb, Saneesh Varghese, Anjana Soman, Jeena Joseph, Krupa Ann Mathew, Godi Raghu, George Thomas, Sreekumar E, Manjula S, Santosh Kumar T. R, Hiroyasu Nakano
    PLoS ONE.2013; 8(4): e59350.     CrossRef
  • Protective and antioxidant role of selenium on arsenic trioxide–induced oxidative stress and genotoxicity in the fish hepatoma cell line PLHC‐1
    Vellaisamy Selvaraj, Mindy Yeager‐Armstead, Elizabeth Murray
    Environmental Toxicology and Chemistry.2012; 31(12): 2861.     CrossRef
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Resveratrol at High Doses Acts as an Apoptotic Inducer in Endothelial Cells
Kyungmin In, Jongbong Park, Heonyong Park
Cancer Res Treat. 2006;38(1):48-53.   Published online February 28, 2006
DOI: https://doi.org/10.4143/crt.2006.38.1.48
AbstractAbstract PDFPubReaderePub
Purposes

Resveratrol is a phenolic compound found in grapes and other food products. In order to assess the availability of resveratrol as an angio-inhibiting drug, we examined whether resveratrol plays an important role in bovine aortic endothelial cells (BAECs) for cell apoptosis and cell migration.

Methods and Materials

Endothelial cell apoptosis was observed as detected by the Hoechst staining and the caspase-3 activity. Additionally, Western blotting was performed for monitoring the activities of various cell signaling molecules.

Results

Resveratrol was shown to act as a pro-apoptotic agent. The pro-apoptotic effect of resveratrol was as great as that of etoposide, a well-known anti-cancer drug. In addition, resveratrol had an inhibitory effect on endothelial cell migration. The demonstrated efficacy of resveratrol suggests that resveratrol may be utilized as an anti-angiogenic drug. To determine the underlying mechanisms, we further investigated which signaling molecules are activated by resveratrol. Extracellular signal-regulated kinase (ERK) was activated by the treatment with resveratrol in BAECs, whereas endothelial nitric oxide synthetase (eNOS), Akt, and Jun N-terminal kinase (JNK) were inhibited. The pretreatment with PD compound, an ERK inhibitor, had no effect on the pro-apoptosis induced by resveratrol.

Conclusion

Resveratrol plays an important role in endothelial cell apoptosis, indicating that resveratrol can be utilized as a potent anti-angiogenic drug.

Citations

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  • Novel plasma-polymerized coating facilitates HeLa cell spheroid formation, exerting necroptosis via β-cyclodextrin-encapsulated resveratrol
    Sujeong Jang, Namwuk Baek, Youngsik Seo, Hyuna Lim, Donggeun Jung, Heonyong Park
    Journal of Analytical Science and Technology.2024;[Epub]     CrossRef
  • Effect of eIF2α in Neuronal Injury Induced by High Glucose and the Protective Mechanism of Resveratrol
    Lijing Zhang, Kaining Zhi, Yanfang Su, Wenpeng Peng, Xianfang Meng
    Molecular Neurobiology.2023; 60(10): 6043.     CrossRef
  • A comparison of resveratrol and other polyphenolic compounds on Notch activation and endothelial cell activity
    Bryce LaFoya, Jordan A. Munroe, Allan R. Albig, Myon-Hee Lee
    PLOS ONE.2019; 14(1): e0210607.     CrossRef
  • Resveratrol-Induced Temporal Variation in the Mechanical Properties of MCF-7 Breast Cancer Cells Investigated by Atomic Force Microscopy
    Jagoba Iturri, Andreas Weber, Alberto Moreno-Cencerrado, Maria dM Vivanco, Rafael Benítez, Stefano Leporatti, José Luis Toca-Herrera
    International Journal of Molecular Sciences.2019; 20(13): 3275.     CrossRef
  • Effect of Fermented Platycodon grandiflorum Extract on Cell Proliferation and Migration in Bovine Aortic Endothelial Cells
    Woosoung Choi, Jina Song, Mi-Hyeon Park, Heui Jong Yu, Heonyong Park
    Journal of Life Science.2016; 26(1): 59.     CrossRef
  • Resveratrol inhibits cell cycle progression by targeting Aurora kinase A and Polo-like kinase 1 in breast cancer cells
    RUBICELI MEDINA-AGUILAR, LAURENCE A. MARCHAT, ELENA ARECHAGA OCAMPO, PATRICIO GARIGLIO, JAIME GARCÍA MENA, NICOLÁS VILLEGAS SEPÚLVEDA, MACARIO MARTÍNEZ CASTILLO, CÉSAR LÓPEZ-CAMARILLO
    Oncology Reports.2016; 35(6): 3696.     CrossRef
  • Autophagy inhibition augments resveratrol-induced apoptosis in Ishikawa endometrial cancer cells
    Tomohiko Fukuda, Katsutoshi Oda, Osamu Wada-Hiraike, Kenbun Sone, Kanako Inaba, Yuji Ikeda, Chinami Makii, Aki Miyasaka, Tomoko Kashiyama, Michihiro Tanikawa, Takahide Arimoto, Tetsu Yano, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
    Oncology Letters.2016; 12(4): 2560.     CrossRef
  • Apoptotic Effect of Pinosylvin at a High Concentration Regulated by c-Jun N-Terminal Kinase in Bovine Aortic Endothelial Cells
    Jina Song, Jinsun Park, Eunsil Jeong, A-Young So, Jaeho Pyee, Heonyong Park
    Journal of Life Science.2015; 25(4): 416.     CrossRef
  • Resveratrol synergistically augments anti-tumor effect of 5-FU in vitro and in vivo by increasing S-phase arrest and tumor apoptosis
    Jiening Dun, Xueyan Chen, Haixia Gao, Yan Zhang, Huajun Zhang, Yongjian Zhang
    Experimental Biology and Medicine.2015; 240(12): 1672.     CrossRef
  • Pinosylvin at a high concentration induces AMPK-mediated autophagy for preventing necrosis in bovine aortic endothelial cells
    Jinsun Park, Jaeho Pyee, Heonyong Park
    Canadian Journal of Physiology and Pharmacology.2014; 92(12): 993.     CrossRef
  • Resveratrol promotes endothelial cell wound healing under laminar shear stress through an estrogen receptor-α-dependent pathway
    Arif Yurdagul, James J. Kleinedler, Marshall C. McInnis, Alok R. Khandelwal, Allyson L. Spence, A. Wayne Orr, Tammy R. Dugas
    American Journal of Physiology-Heart and Circulatory Physiology.2014; 306(6): H797.     CrossRef
  • Protective Effects of Resveratrol on TNF-α-Induced Endothelial Cytotoxicity in Baboon Femoral Arterial Endothelial Cells
    Juan Xiao, Jun Song, Vida Hodara, Allen Ford, Xing Li Wang, Qiang Shi, Li Chen, John L. VandeBerg
    Journal of Diabetes Research.2013; 2013: 1.     CrossRef
  • Synergistic anti-proliferative effect of resveratrol and etoposide on human hepatocellular and colon cancer cell lines
    Fatemehsadat Amiri, Amir-Hassan Zarnani, Hamid Zand, Fariba Koohdani, Mahmood Jeddi-Tehrani, Mohammadreza Vafa
    European Journal of Pharmacology.2013; 718(1-3): 34.     CrossRef
  • Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity
    Vittorio Calabrese, Carolin Cornelius, Albena T. Dinkova-Kostova, Ivo Iavicoli, Rosanna Di Paola, Aleardo Koverech, Salvatore Cuzzocrea, Enrico Rizzarelli, Edward J. Calabrese
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2012; 1822(5): 753.     CrossRef
  • Ameliorative Effects of Resveratrol on Acute Ovarian Toxicity Induced by Total Body Irradiation in Young Adult Rats
    Yavuz Simsek, Simay Gurocak, Yusuf Turkoz, Nusret Akpolat, Onder Celik, Ali Ozer, Ercan Yılmaz, Ugur Turhan, Fatma Ozyalin
    Journal of Pediatric and Adolescent Gynecology.2012; 25(4): 262.     CrossRef
  • Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development
    Lindsay Peltz, Jessica Gomez, Maribel Marquez, Frances Alencastro, Negar Atashpanjeh, Tara Quang, Thuy Bach, Yuanxiang Zhao, Antonio Paolo Beltrami
    PLoS ONE.2012; 7(5): e37162.     CrossRef
  • Resveratrol reduces oxidative stress and cell death and increases mitochondrial antioxidants and XIAP in PC6.3-cells
    Minna Kairisalo, Alessandra Bonomo, Alise Hyrskyluoto, Giuseppa Mudò, Natale Belluardo, Laura Korhonen, Dan Lindholm
    Neuroscience Letters.2011; 488(3): 263.     CrossRef
  • Effect of resveratrol on endothelial cell function: Molecular mechanisms
    Christoph A. Schmitt, Elke H. Heiss, Verena M. Dirsch
    BioFactors.2010; 36(5): 342.     CrossRef
  • Dose-Dependency of Resveratrol in Providing Health Benefits
    Subhendu Mukherjee, Jocelyn I. Dudley, Dipak K. Das
    Dose-Response.2010;[Epub]     CrossRef
  • Resveratrol commonly displays hormesis: Occurrence and biomedical significance
    Edward J Calabrese, Mark P Mattson, Vittorio Calabrese
    Human & Experimental Toxicology.2010; 29(12): 980.     CrossRef
  • Biochemical characterization of the lipid-binding properties of a broccoli cuticular wax-associated protein, WAX9D, and its application
    Sun-Young Ahn, Jong-Min Kim, Jae-Ho Pyee, Heon-Yong Park
    BMB Reports .2009; 42(6): 367.     CrossRef
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Pattern of Apoptosis by NS398, a Selective COX-2 Inhibitor, in Hepatocellular Carcinoma Cell Lines
Mi Kyung Park, Moon Kyu Kim, Jung Chul Kim, Young Kwan Sung
Cancer Res Treat. 2005;37(5):313-317.   Published online October 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.5.313
AbstractAbstract PDFPubReaderePub
Purpose

NS398, a selective COX-2 inhibitor, is known to inhibit the growth of COX-2 expressing hepatocellular carcinoma cells. The present study investigated whether the cytotoxic effect of NS398 was COX-2 dependent and whether caspases were involved in NS398-induced apoptosis in hepatocellular carcinoma cells.

Materials and Methods

The expressions of COX-2 in SNU 423 and SNU 449 hepatocellular carcinoma cell lines were examined using RT-PCR and Western blot. The cytotoxic effect of NS398 was measured using MTT in the presence or absence of caspase inhibitors. The distribution of the cell cycle and extent of apoptosis were analyzed using flow cytometry and a Cell Death Elisa kit, respectively.

Results

The expression of COX-2 was observed in SNU423 cells, but not in SNU 449 cells. NS398 treatment resulted in both dose-and time-dependent growth inhibitions, with increases in apoptotic cells in both cell lines. Treatment with the pan-caspase inhibitor, z-VAD- fmk, or the caspase-3 inhibitor, Ac-DMQD-CHO, showed no attenuation of the cytotoxic effect of NS398 in either cell line.

Conclusion

This study demonstrated that the cytotoxic effect of NS398 was independent of COX-2 expression. Caspases were also shown not to be involved in NS398-induced apoptosis in either SNU 423 or SNU 449 Korean HCC cell lines. Our data suggests the feasibility of preventing hepatocellular carcinoma with the use of COX-2 inhibitors needs to be carefully evaluated.

Citations

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  • First study on the immunohistochemical expression of cyclooxygenase-2 and clinicopathological association in canine hepatoid gland neoplasms
    Pinkarn Chantawong, Thanongsak Mamom, Sahatchai Tangtrongsup, Setthakit Chitsanoor, Hassadin Boonsriroj
    Veterinary World.2022; : 2432.     CrossRef
  • Evaluation of Cytotoxicity Effects of Chalcone Epoxide Analogues as a Selective COX-II Inhibitor in the Human Liver Carcinoma Cell Line
    Bahram Daraei, Gholamreza Karimi, Pouran Makhdoumi, Afshin Zarghi
    Journal of Pharmacopuncture.2017; 20(3): 207.     CrossRef
  • RETRACTED ARTICLE: Effect of NS-398, a cyclooxygenase-2 selective inhibitor, on the cytotoxicity of cytotoxic T lymphocytes to ovarian carcinoma cells
    Xinyan Wang, Yu Liang, Jun Wang, Min Wang
    Tumor Biology.2013; 34(3): 1517.     CrossRef
  • Gene Expression Profile of Coronary Artery Cells Treated With Nonsteroidal Anti-inflammatory Drugs Reveals Off-target Effects
    Sanjeewani T. Palayoor, Molykutty J-Aryankalayil, Adeola Y. Makinde, David Cerna, Michael T. Falduto, Scott R. Magnuson, C. Norman Coleman
    Journal of Cardiovascular Pharmacology.2012; 59(6): 487.     CrossRef
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Tetraarsenic Oxide-mediated Apoptosis in a Cervical Cancer Cell Line, SiHa
Jeong Kim, Su-Mi Bae, Dae-Seog Lim, Sun-Young Kwak, Chang-Ki Lee, Yong-Seok Lee, IL-Ju Bae, Jin-Young Yoo, Young-Joo Lee, Chong-Kook Kim, Woong-Shick Ahn
Cancer Res Treat. 2005;37(5):307-312.   Published online October 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.5.307
Retraction in: Cancer Res Treat 2007;39(1):48
  • 14,008 View
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Proteome Analysis of Differential Protein Expression in Cervical Cancer Cells after Paclitaxel Treatment
Eun-Kyoung Yim, Jun-Sang Bae, Seung-Bak Lee, Keun-Ho Lee, Chan-Joo Kim, Sung-Eun Namkoong, Soo-Jong Um, Jong-Sup Park
Cancer Res Treat. 2004;36(6):395-399.   Published online December 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.6.395
AbstractAbstract PDFPubReaderePub
Purpose

It is well known that infection with HPV (human papillomavirus) is the main cause of cervical cancer and certain types of HPV are recognized as carcinogens. At present, there is little information regarding the antineoplastic mechanism of paclitaxel against cervical carcinoma cells. We thus tried to analyze differential protein expression and antineoplastic mechanism-related proteins after paclitaxel treatment on cervical cancer cells by using a proteomic analysis and to investigate the mechanism of action.

Materials and Methods

Using proteomics analysis including 2-DE and MALDI-TOF-MS, we detected the antineoplastic mechanism-related proteins. Then, we performed western blot analysis for apoptosis- and transformation-related proteins to confirm expression patterns derived from proteome analysis after paclitaxel treatment.

Results

We identified several cellular proteins that are responsive to paclitaxel treatment in HeLa cells using proteomics methods. Paclitaxel treatment elevated mainly apoptosis, immune response and cell cycle check point-related proteins. On the other hand, paclitaxel treatment diminished growth factor/oncogene-related proteins and transcription regulation-related proteins. Also, in the HPV-associated cervical carcinoma cells, paclitaxel demonstrated anti-proliferative activity through the membrane death receptor-mediated apoptotic pathway and the mitochondrial-mediated pathway.

Conclusion

Identification and characterization of functionally modulated proteins involved in anti-cancer regulatory events should lead to a better understanding of the long-term actions of paclitaxel at the molecular level and will contribute to the future development of novel therapeutic drug treatments based upon current therapies.

Citations

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  • Proteomic Analysis of Thermus thermophilus Cells after Treatment with Antimicrobial Peptide
    Alexey K. Surin, Anna I. Malykhina, Michail V. Slizen, Alexey P. Kochetov, Mariya Yu. Suvorina, Vadim E. Biryulyov, Sergei Y. Grishin, Oxana V. Galzitskaya
    Bacteria.2024; 3(4): 299.     CrossRef
  • Proteomics approaches in cervical cancer: focus on the discovery of biomarkers for diagnosis and drug treatment monitoring
    Georgia Kontostathi, Jerome Zoidakis, Nicholas P. Anagnou, Kalliopi I. Pappa, Antonia Vlahou, Manousos Makridakis
    Expert Review of Proteomics.2016; 13(8): 731.     CrossRef
  • PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer
    Haiyan Zhu, Jun Wu, Wenwen Zhang, Hui Luo, Zhaojun Shen, Huihui Cheng, Xueqiong Zhu
    Scientific Reports.2016;[Epub]     CrossRef
  • Proteomic Analysis of Anticancer TCMs Targeted at Mitochondria
    Yang Wang, Ru-Yuan Yu, Qing-Yu He
    Evidence-Based Complementary and Alternative Medicine.2015; 2015: 1.     CrossRef
  • Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture
    Debasish Paul, Avinash Kumar, Akshada Gajbhiye, Manas K. Santra, Rapole Srikanth
    BioMed Research International.2013; 2013: 1.     CrossRef
  • Identification of Cervical Cancer Proteins Associated With Treatment With Paclitaxel and Cisplatin in Patients
    Huiling Liu, Yin Han, Ruoran Mi, Ying Zhang, Gang Su, Hailin Wang, Xin Zhou, Xiangwen Liu, Bingdong Zhu
    International Journal of Gynecological Cancer.2011; 21(8): 1452.     CrossRef
  • Impact of taxol on dermal papilla cells — A proteomics and bioinformatics analysis
    Pei-Hsiu Chen, Chih-Yuan Wang, Ching-Wu Hsia, Ming-Yi Ho, Ann Chen, Min-Jen Tseng, Yung-Fu Wu, Han-Min Chen, Tzu-Hao Huang, Hung-Te Liu, Hao-Ai Shui
    Journal of Proteomics.2011; 74(12): 2760.     CrossRef
  • 10,679 View
  • 64 Download
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Phenylacetate Induces Growth Inhibition and Apoptosis of Human Osteosarcoma Cells
Jong Hyuk Park, Min Young Park, Ho Sung Park, Kyu Yun Jang, Myoung Ja Chung, Woo Sung Moon, Dong Geun Lee, Myoung Jae Kang
Cancer Res Treat. 2004;36(5):324-329.   Published online October 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.5.324
AbstractAbstract PDFPubReaderePub
Purpose

Phenylacetate has potent antiproliferative effects in many malignant tumors. However, the exact mechanism as to how phenylacetate induces cell growth arrest remains unclear and very little is known about its effects on human osteosarcoma cells. In this study, we investigated whether phenylacetate is effective against two osteosarcoma cell lines (HOS and U-2 OS) in vitro.

Materials and Methods

The viability of phenylacetate-treated cell lines was assessed by trypan blue exclusion assay, and the cell cycle distribution was measured by flow cytometry. To measure cell apoptosis, poly (ADP-ribose) polymerase cleavage assay and flow cytometry were employed. The expressions of cell cycle-regulatory proteins and the apoptosis-related genes were evaluated by western blot analysis.

Results

Phenylacetate was found to inhibit the growth of osteosarcoma cells, induce cell cycle arrest in the G1 phase, and induce apoptosis. A significant decrease in Bcl-2 expression and a mild up-regulation of Bax were also observed in both phenylacetate-treated cell lines. Reduced phosphorylation of the pRb and the increased expression of p21Cip1 were observed subsequent to treatment with phenylacetate.

Conclusion

These findings support the idea that phenylacetate may be an effective chemotherapeutic agent to be employed in the future against osteosarcoma, because phenylacetate acts to inhibit the growth of osteosarcoma cells through cell cycle arrest and apoptosis.

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  • Evaluation of α-hydroxycinnamic acids as pyruvate carboxylase inhibitors
    Daniel J. Burkett, Brittney N. Wyatt, Mallory Mews, Anson Bautista, Ryan Engel, Chris Dockendorff, William A. Donaldson, Martin St. Maurice
    Bioorganic & Medicinal Chemistry.2019; 27(18): 4041.     CrossRef
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  • 45 Download
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Activity of Green Tea Polyphenol Epigallocatechin-3-gallate Against Ovarian Carcinoma Cell Lines
Yong Wook Kim, Su Mi Bae, Joon Mo Lee, Sung Eun Namkoong, Sei Jun Han, Byoung Rai Lee, Insu P. Lee, Sang Hee Kim, Young Joo Lee, Chong Kook Kim, Yong-Wan Kim, Woong Shick Ahn
Cancer Res Treat. 2004;36(5):315-323.   Published online October 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.5.315
AbstractAbstract PDFPubReaderePub
Purpose

A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG), is known to possess anti-cancer properties. In this study, the time-course of the anticancer effects of EGCG on human ovarian cancer cells were investigated to provide insights into the molecular-level understanding of the growth suppression mechanism involved in EGCG-mediated apoptosis and cell cycle arrest.

Materials and Methods

Three human ovarian cancer cell lines (p53 negative, SKOV-3 cells; mutant type p53, OVCAR-3 cells; and wild type p53, PA-1 cells) were used. The effect of EGCG treatment was studied via a cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay.

Results

EGCG exerts a significant role in suppressing ovarian cancer cell growth, showed dose dependent growth inhibitory effects in each cell line and induced apoptosis and cell cycle arrest. The cell cycle was arrested at the G1 phase by EGCG in SKOV-3 and OVCAR-3 cells.

In contrast, the cell cycle was arrested in the G1/S phase in PA-1 cells. EGCG differentially regulated the expression of genes and proteins (Bax, p21, Retinoblastoma, cyclin D1, CDK4 and Bcl-XL) more than 2 fold, showing a possible gene regulatory role for EGCG. The continual expression in p21WAF1 suggests that EGCG acts in the same way with p53 proteins to facilitate apoptosis after EGCG treatment. Bax, PCNA and Bcl-X are also important in EGCG-mediated apoptosis. In contrast, CDK4 and Rb are not important in ovarian cancer cell growth inhibition.

Conclusion

EGCG can inhibit ovarian cancer cell growth through the induction of apoptosis and cell cycle arrest, as well as in the regulation of cell cycle related proteins. Therefore, EGCG-mediated apoptosis could be applied to an advanced strategy in the development of a potential drug against ovarian cancer.

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  • Role of Epigallocatechin Gallate in Selected Malignant Neoplasms in Women
    Anna Markowska, Michał Antoszczak, Janina Markowska, Adam Huczyński
    Nutrients.2025; 17(2): 212.     CrossRef
  • Epigallocatechin 3-gallate: From green tea to cancer therapeutics
    Manzar Alam, Sabeeha Ali, Ghulam Md. Ashraf, Anwar L. Bilgrami, Dharmendra Kumar Yadav, Md. Imtaiyaz Hassan
    Food Chemistry.2022; 379: 132135.     CrossRef
  • Synergistic effects of green tea extract and paclitaxel in the induction of mitochondrial apoptosis in ovarian cancer cell lines
    Mohammad Panji, Vahideh Behmard, Zahra Zare, Monireh Malekpour, Hasan Nejadbiglari, Saeede Yavari, Tina Nayerpour dizaj, Azadeh Safaeian, Ali Bakhshi, Omid Abazari, Mojtaba Abbasi, Parisa Khanicheragh, Maryam Shabanzadeh
    Gene.2021; 787: 145638.     CrossRef
  • A Review on the Biological Activity of Camellia Species
    Ana Margarida Teixeira, Clara Sousa
    Molecules.2021; 26(8): 2178.     CrossRef
  • Estrogenic biological activity and underlying molecular mechanisms of green tea constituents
    Ryoiti Kiyama
    Trends in Food Science & Technology.2020; 95: 247.     CrossRef
  • Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells
    Rhiane Moody, Kirsty Wilson, Anthony Jaworowski, Magdalena Plebanski
    Cancers.2020; 12(3): 673.     CrossRef
  • Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer
    Saleh A. Almatroodi, Ahmad Almatroudi, Amjad Ali Khan, Fahad A. Alhumaydhi, Mohammed A. Alsahli, Arshad Husain Rahmani
    Molecules.2020; 25(14): 3146.     CrossRef
  • The Potential Roles of Epigallocatechin-3-Gallate in the Treatment of Ovarian Cancer: Current State of Knowledge


    Sabrina Bimonte, Marco Cascella
    Drug Design, Development and Therapy.2020; Volume 14: 4245.     CrossRef
  • Bioinformatics Analysis on Molecular Mechanism of Green Tea Compound Epigallocatechin‐3‐Gallate Against Ovarian Cancer
    S Xinqiang, Z Mu, C Lei, LY Mun
    Clinical and Translational Science.2017; 10(4): 302.     CrossRef
  • Pharmacological profile of green tea and its polyphenols: a review
    Sumit Bansal, Navneet Syan, Pooja Mathur, Shivani Choudhary
    Medicinal Chemistry Research.2012; 21(11): 3347.     CrossRef
  • Plant phytochemicals as new potential drugs for immune disorders and cancer therapy: really a promising path?
    Salvatore Chirumbolo
    Journal of the Science of Food and Agriculture.2012; 92(8): 1573.     CrossRef
  • Green tea for ovarian cancer prevention and treatment: A systematic review of the in vitro, in vivo and epidemiological studies
    Dominique Trudel, David P. Labbé, Isabelle Bairati, Vincent Fradet, Laurent Bazinet, Bernard Têtu
    Gynecologic Oncology.2012; 126(3): 491.     CrossRef
  • Tea Consumption and Epithelial Ovarian Cancer Risk: A Systematic Review of Observational Studies
    Sarah J. Oppeneer, Kim Robien
    Nutrition and Cancer.2011; 63(6): 817.     CrossRef
  • 10,638 View
  • 64 Download
  • 13 Crossref
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Comparison of As2O3 and As4O6 in the Detection of SiHa Cervical Cancer Cell Growth Inhibition Pathway
Yong Wook Kim, Su Mi Bae, Keun Ho Lee, Joon Mo Lee, Sung Eun Namkoong, Insu P. Lee, Chong Kook Kim, Jeong-Sun Seo, Jeong-Im Sin, Yong-Wan Kim, Woong Shick Ahn
Cancer Res Treat. 2004;36(4):255-262.   Published online August 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.4.255
Retraction in: Cancer Res Treat 2007;39(1):47
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Synthetic CDCA Derivatives-Induced Apoptosis of Stomach Cancer Cell Line SNU-1 Cells
Bongkyung Moon, Min-Chan Kim, Joo-sung Park
Cancer Res Treat. 2004;36(2):132-139.   Published online April 30, 2004
DOI: https://doi.org/10.4143/crt.2004.36.2.132
AbstractAbstract PDFPubReaderePub
Purpose

This study was conducted to explore whether CDCA derivatives induce apoptosis in a stomach cancer cell line, and to dissect the detailed mechanism underlying apoptosis.

Materials and Methods

The human stomach cancer cell line, SNU-1, cells were treated with the synthetic CDCA derivatives, HS-1199 and HS-1200. DNA and mitochondrial stains were used to detect apoptotic cells by fluorescence imaging or flow cytometry. The caspase-3 activity was measured by Western blotting.

Results

Both the HS-1199 and HS-1200 induced decreased viabilities of the SNU-1 cells, in time-dependent manners. The CDCA derivatives demonstrated various apoptosis hallmarks, such as mitochondrial changes (reduction of MMP, cytochrome c release, and Smac/ DIABLO translocation), activation of caspase-3 (resulting in the degradation of PARP and DFF45), DNA fragmentation and nuclear condensation.

Conclusion

The CDCA derivatives, HS-1199 and HS-1200, both induced apoptosis of the SNU-1 gastric cancer cells in caspase- and mitochondria-dependent fashions. Many important issues relating to their therapeutic applications remain to be elucidated.

Citations

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  • The anticancer activity of bile acids in drug discovery and development
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