Skip Navigation
Skip to contents

Cancer Res Treat : Cancer Research and Treatment

OPEN ACCESS

Search

Page Path
HOME > Search
4 "Histone deacetylase inhibitor"
Filter
Filter
Article category
Keywords
Publication year
Authors
Funded articles
Original Articles
Lung and Thoracic cancer
Histone Deacetylase as a Valuable Predictive Biomarker and Therapeutic Target in Immunotherapy for Non-Small Cell Lung Cancer
Hyun-Seock Shin, Juwhan Choi, Jinhwan Lee, Sung Yong Lee
Cancer Res Treat. 2022;54(2):458-468.   Published online September 10, 2021
DOI: https://doi.org/10.4143/crt.2021.425
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Histone deacetylase inhibitors (HDACis) are epigenetic regulators and used clinically for hematopoietic malignancies. Recently, HDACis have received attention as a factor that modulates the immune system. In this study, the role of histone deacetylase (HDAC) expression as a predictive marker in lung cancer patients who were treated with immune checkpoint inhibitors (ICIs) and the role of HDACi and ICI combination treatment in the mouse tumor model were analyzed.
Materials and Methods
The overall response rate (ORR) and progression-free survival (PFS) were analyzed by the expression of HDAC. In vitro assay, the mRNA and protein expression levels of cytokines and programmed death-ligand 1 (PD-L1) were analyzed after HDACi treatment. In vivo assay, TC-1 tumor-bearing mice were treated with HDACi and mouse programmed cell death 1 (PD-1) inhibitor.
Results
The HDAC6 low expression group showed high ORR and prolonged PFS. When the selective HDAC6 inhibitor was administered to the A549 cell line, the levels of interleukin-1β and interleukin-6 decreased and the expression of PD-L1 was reduced. Mice that received both the mouse PD-1 inhibitor and pan-HDACi had a smaller tumor size than that of the mice from the control group. Moreover, mice treated with the mouse PD-1 inhibitor and pan-HDACi generated greater numbers of E7-specific CD8+ T cells.
Conclusion
HDAC6 expression can predict the prognosis of non–small cell lung cancerpatients who were treated with ICIs. Furthermore, co-treatment with HDACi and PD-1 inhibitor was shown to decrease the tumor growth rate and create a favorable tumor microenvironment for cytotoxic T lymphocytes in the TC-1 mouse model.

Citations

Citations to this article as recorded by  
  • Immunomodulatory properties of HDAC6 inhibitors in cancer diseases: New chances for sophisticated drug design and treatment optimization
    Bernhard Biersack, Bianca Nitzsche, Michael Höpfner
    Seminars in Cell & Developmental Biology.2024; 154: 286.     CrossRef
  • Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1
    Ana Dillen, Indy Bui, Megan Jung, Stephanie Agioti, Apostolos Zaravinos, Benjamin Bonavida
    Cancers.2024; 16(6): 1237.     CrossRef
  • Reducing PD-L1 Expression by Degraders and Downregulators as a Novel Strategy to Target the PD-1/PD-L1 Pathway
    Zhijie Wang, Lin Yuan, Xiaotong Liao, Xia Guo, Jianjun Chen
    Journal of Medicinal Chemistry.2024; 67(8): 6027.     CrossRef
  • Dual molecule targeting HDAC6 leads to intratumoral CD4+ cytotoxic lymphocytes recruitment through MHC-II upregulation on lung cancer cells
    Sarah Ducellier, Mélanie Demeules, Boris Letribot, Massimiliano Gaetani, Chloé Michaudel, Harry Sokol, Abdallah Hamze, Mouad Alami, Mégane Nascimento, Sébastien Apcher
    Journal for ImmunoTherapy of Cancer.2024; 12(4): e007588.     CrossRef
  • Selective HDAC6 Inhibition Has the Potential for Anti-Cancer Effect in Renal Cell Carcinoma
    Tsutomu Anraku, Masaki Murata, Hiroo Kuroki, Akira Kazama, Yuko Shirono, Masayuki Tasaki, Vladimir Bilim, Yoshihiko Tomita
    Journal of Personalized Medicine.2024; 14(7): 704.     CrossRef
  • Histone deacetylase inhibitors for leukemia treatment: current status and future directions
    Mohammad-Salar Hosseini, Zohreh Sanaat, Mohammad Amin Akbarzadeh, Yosra Vaez-Gharamaleki, Mahsa Akbarzadeh
    European Journal of Medical Research.2024;[Epub]     CrossRef
  • Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma
    Hikaru Nanamori, Yu Sawada
    International Journal of Molecular Sciences.2022; 23(3): 1119.     CrossRef
  • Epigenetic Alterations and Inflammation as Emerging Use for the Advancement of Treatment in Non-Small Cell Lung Cancer
    Shuo Yang, Yang Huang, Qi Zhao
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance
    Hyein Jo, Kyeonghee Shim, Dooil Jeoung
    International Journal of Molecular Sciences.2022; 23(17): 9592.     CrossRef
  • Epigenetic modifications: Critical participants of the PD‑L1 regulatory mechanism in solid tumors (Review)
    Xiaoran Ma, Jibiao Wu, Bin Wang, Cun Liu, Lijuan Liu, Changgang Sun
    International Journal of Oncology.2022;[Epub]     CrossRef
  • 7,191 View
  • 212 Download
  • 10 Web of Science
  • 10 Crossref
Close layer
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.

Citations

Citations to this article as recorded by  
  • 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
  • 15,267 View
  • 213 Download
  • 4 Web of Science
  • 4 Crossref
Close layer
Sequence-Dependent Radiosensitization of Histone Deacetylase Inhibitors Trichostatin A and SK-7041
Jin Ho Kim, Il Han Kim, Jin Hee Shin, Hak Jae Kim, In Ah Kim
Cancer Res Treat. 2013;45(4):334-342.   Published online December 31, 2013
DOI: https://doi.org/10.4143/crt.2013.45.4.334
AbstractAbstract PDFPubReaderePub
PURPOSE
This preclinical study is to determine whether the capacity of histone deacetylase (HDAC) inhibitors to enhance radiation response depends on temporal sequences of HDAC inhibition and irradiation.
MATERIALS AND METHODS
The effects of HDAC inhibitors trichostatin A (TSA) and SK-7041 on radiosensitivity in human lung cancer cells were examined using a clonogenic assay, exposing cells to HDAC inhibitors in various sequences of HDAC inhibition and radiation. We performed Western blot of acetylated histone H3 and flow cytometry to analyze cell cycle phase distribution.
RESULTS
TSA and SK-7041 augmented radiation cell lethality in an exposure time-dependent manner when delivered before irradiation. The impact of TSA and SK-7041 on radiosensitivity rapidly diminished when HDAC inhibition was delayed after irradiation. Radiation induced the acetylation of histone H3 in cells exposed to TSA, while irradiation alone had no effect on the expression of acetylated histone H3 in TSA-naive cells. Preirradiation exposure to TSA abrogated radiation-induced G2/M-phase arrest. When delivered after irradiation, TSA had no effect on the peak of radiation-induced G2/M-phase arrest.
CONCLUSION
TSA and SK-7041 enhances radiosensitivity only when delivered before irradiation. Unless proven otherwise, it seems prudent to apply scheduling including preirradiation HDAC inhibition so that maximal radiosensitization is obtained.

Citations

Citations to this article as recorded by  
  • Mechanistic Sequence of Histone Deacetylase Inhibitors and Radiation Treatment: An Overview
    Elsie Neo Seane, Shankari Nair, Charlot Vandevoorde, Anna Joubert
    Pharmaceuticals.2024; 17(5): 602.     CrossRef
  • Investigation of geroprotective and radioprotective effects of berberine and trichostatin A on the model of Drosophila melanogaster
    N. Ulyasheva, E. Proshkina, M. Shaposhnikov, A. Moskalev
    Proceedings of the Komi Science Centre of the Ural Division of the Russian Academy of Sciences.2023; 0(6): 93.     CrossRef
  • Low Dose of Trichostatin A Improves Radiation Resistance by Activating Akt/Nrf2-Dependent Antioxidation Pathway in Cancer Cells
    Fengqiu Zhang, Changsheng Shao, Zhu Chen, Yalin Li, Xumiao Jing, Qing Huang
    Radiation Research.2021;[Epub]     CrossRef
  • Time-sequential change in immune-related gene expression after irradiation in glioblastoma: next-generation sequencing analysis
    Yi-Jun Kim, Kwangsoo Kim, Soo Yeon Seo, Juyeon Yu, Il Han Kim, Hak Jae Kim, Chul-Kee Park, Kye Hwa Lee, Junjeong Choi, Myung Seon Song, Jin Ho Kim
    Animal Cells and Systems.2021; 25(4): 245.     CrossRef
  • Is level of acetylation directly correlated to radiation sensitivity of cancer cell?
    Fengqiu Zhang, Zhu Chen, Changsheng Shao, Qing Huang
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis.2019; 813: 13.     CrossRef
  • 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 Research and Treatment.2019; 51(2): 696.     CrossRef
  • Psammaplin A-Modified Novel Radiosensitizers for Human Lung Cancer and Glioblastoma Cells
    Chan Woo Wee, Jin Ho Kim, Hak Jae Kim, Hyun-Cheol Kang, Soo Youn Suh, Beom Soo Shin, Eunsook Ma, Il Han Kim
    Journal of Radiation Protection and Research.2019; 44(1): 15.     CrossRef
  • Isotype-Specific Inhibition of Histone Deacetylases: Identification of Optimal Targets for Radiosensitization
    Jin Ho Kim, Sung Ho Moon, Mina No, Jae Jin Kim, Eun Jung Choi, Bong Jun Cho, Jae Sung Kim, Il Han Kim, In Ah Kim
    Cancer Research and Treatment.2016; 48(3): 1130.     CrossRef
  • 12,619 View
  • 47 Download
  • 6 Web of Science
  • 8 Crossref
Close layer
A Histone Deacetylase Inhibitor, Trichostatin A, Enhances Radiosensitivity by Abrogating G2/M Arrest in Human Carcinoma Cells
In Ah Kim, Jin Ho Kim, Jin Hee Shin, Il Han Kim, Jae Sung Kim, Hong-Gyun Wu, Eui Kyu Chie, Yong Ho Kim, Bo-Kyung Kim, Semie Hong, Seok Won Park, Sung Whan Ha, Charn Il Park
Cancer Res Treat. 2005;37(2):122-128.   Published online April 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.2.122
AbstractAbstract PDFPubReaderePub
Purpose

Histone deacetylase inhibitors (HDIs) are emerging as potentially useful components in anticancer therapy. In this study, we tried to confirm the radiosensitizing effect of trichostatin A (TSA) on a panel of human carcinoma cell lines and elucidate its mechanism of interaction.

Materials and Methods

A549, HeLa and Caski cells were exposed to TSA for 18 hr prior to irradiation, and the cell survival then measured using a clonogenic assay. Western blot and flow cytometric analyses, for histone acetylation, and cell cycle and apoptosis, respectively, were also performed.

Results

TSA increased the acetylation of histone H3. The pretreatment of TSA consistently radiosensitized all three cell lines. The SF2 (surviving fraction at 2 Gy) of TSA-treated cells was significantly lower than that of mock treated cells. The SER (sensitizer enhancement ratio) increased in all 3 cell lines, in concentration dependent manners. The TSA treated cells showed abrogation of radiation-induced G2/M arrest, in a concentration dependent manner.

Conclusion

The pretreatment of TSA enhanced the radiosensitivity of a panel of human carcinoma cells, which was attributed, in part, to the abrogation of radiation-induced G2/M arrest.

Citations

Citations to this article as recorded by  
  • Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
    Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Radiosensitizing effect of dendrosomal nanoformulation of curcumin on cancer cells
    Tahereh Jalali Varnamkhasti, Meisam Jafarzadeh, Majid Sadeghizadeh, Mahdi Aghili
    Pharmacological Reports.2022; 74(4): 718.     CrossRef
  • Pharmacological Properties of Trichostatin A, Focusing on the Anticancer Potential: A Comprehensive Review
    Abdelhakim Bouyahya, Nasreddine El Omari, Mohamed Bakha, Tarik Aanniz, Naoual El Menyiy, Naoufal El Hachlafi, Aicha El Baaboua, Mohamed El-Shazly, Mohammed Merae Alshahrani, Ahmed Abdullah Al Awadh, Learn-Han Lee, Taoufiq Benali, Mohammad S. Mubarak
    Pharmaceuticals.2022; 15(10): 1235.     CrossRef
  • Low Dose of Trichostatin A Improves Radiation Resistance by Activating Akt/Nrf2-Dependent Antioxidation Pathway in Cancer Cells
    Fengqiu Zhang, Changsheng Shao, Zhu Chen, Yalin Li, Xumiao Jing, Qing Huang
    Radiation Research.2021;[Epub]     CrossRef
  • Targeted Therapeutic Strategies for Triple-Negative Breast Cancer
    Ying Li, Zhijun Zhan, Xuemin Yin, Shujun Fu, Xiyun Deng
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Is level of acetylation directly correlated to radiation sensitivity of cancer cell?
    Fengqiu Zhang, Zhu Chen, Changsheng Shao, Qing Huang
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis.2019; 813: 13.     CrossRef
  • Synergistic antitumor interaction between valproic acid, capecitabine and radiotherapy in colorectal cancer: critical role of p53
    Manuela Terranova-Barberio, Biagio Pecori, Maria Serena Roca, Serena Imbimbo, Francesca Bruzzese, Alessandra Leone, Paolo Muto, Paolo Delrio, Antonio Avallone, Alfredo Budillon, Elena Di Gennaro
    Journal of Experimental & Clinical Cancer Research.2017;[Epub]     CrossRef
  • Histone Acetylation Induced Transformation of B-DNA to Z-DNA in Cells Probed through FT-IR Spectroscopy
    Fengqiu Zhang, Qing Huang, Jingwen Yan, Zhu Chen
    Analytical Chemistry.2016; 88(8): 4179.     CrossRef
  • Cell-based multi-substrate assay coupled to UHPLC-ESI-MS/MS for a quick identification of class-specific HDAC inhibitors
    Vincent Zwick, Claudia Simões-Pires, Muriel Cuendet
    Journal of Enzyme Inhibition and Medicinal Chemistry.2016; 31(sup1): 209.     CrossRef
  • Assessment of the Effect of Trichostatin A on HeLa Cells through FT-IR Spectroscopy
    Fengqiu Zhang, Qing Huang, Jingwen Yan, Xin Zhang, Jianxin Li
    Analytical Chemistry.2015; 87(4): 2511.     CrossRef
  • Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), enhances anti-tumor effects of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in triple-negative breast cancer cells
    Ahrum Min, Seock-Ah Im, Debora Keunyoung Kim, Sang-Hyun Song, Hee-Jun Kim, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Do-Youn Oh, Tae-You Kim, Mark J O’Connor, Yung-Jue Bang
    Breast Cancer Research.2015;[Epub]     CrossRef
  • CD44 is a biomarker associated with human prostate cancer radiation sensitivity
    WeiWei Xiao, Peter H. Graham, Carl A. Power, Jingli Hao, John H. Kearsley, Yong Li
    Clinical & Experimental Metastasis.2012; 29(1): 1.     CrossRef
  • Identification of a radiosensitivity signature using integrative metaanalysis of published microarray data for NCI-60 cancer cells
    Han Sang Kim, Sang Cheol Kim, Sun Jeong Kim, Chan Hee Park, Hei-Cheul Jeung, Yong Bae Kim, Joong Bae Ahn, Hyun Cheol Chung, Sun Young Rha
    BMC Genomics.2012;[Epub]     CrossRef
  • In vivoRadiosensitization Effect of HDAC Inhibitor, SK-7041 on RIF-1 Cell Line
    Eui Kyu Chie, Jin Hee Shin, In Ah Kim, Il Han Kim
    The Journal of the Korean Society for Therapeutic Radiology and Oncology.2010; 28(4): 219.     CrossRef
  • Epigenetic modulation of radiation response in human cancer cells with activated EGFR or HER-2 signaling: Potential role of histone deacetylase 6
    In Ah Kim, Mina No, Jang Mi Lee, Jin Hee Shin, Jee Sun Oh, Eun Jung Choi, Il Han Kim, Peter Atadja, Eric J. Bernhard
    Radiotherapy and Oncology.2009; 92(1): 125.     CrossRef
  • Histone Deacetylase Inhibitor–Mediated Radiosensitization of Human Cancer Cells: Class Differences and the Potential Influence of p53
    In Ah Kim, Jin Hee Shin, Il Han Kim, Jin Ho Kim, Jae Sung Kim, Hong Gyun Wu, Eui Kyu Chie, Sung Whan Ha, Charn Il Park, Gary D. Kao
    Clinical Cancer Research.2006; 12(3): 940.     CrossRef
  • 12,464 View
  • 73 Download
  • 16 Crossref
Close layer

Cancer Res Treat : Cancer Research and Treatment
Close layer
TOP