Cancer Research and Treatment

Original Articles

CNS cancer

CYBC1 Drives Glioblastoma Progression via Reactive Oxygen Species and NF-κB Pathways: Hyeon Ji Kim, Tae-Jun Kim, Jin-Hwa Cho, Mee-Seon Kim, Jin-Seok Byun, Do-Yeon Kim; Cancer Res Treat. 2025;57(4):951-967. Published online December 24, 2024; DOI: https://doi.org/10.4143/crt.2024.827

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aims to investigate the role of cytochrome b-245 chaperone 1 (CYBC1) in glioblastoma (GBM) progression, focusing on its involvement in reactive oxygen species (ROS) production and associated signaling pathways. Understanding the molecular mechanisms driven by CYBC1 could provide new therapeutic targets and prognostic markers for GBM.
Materials and Methods
Publicly available datasets were analyzed to assess CYBC1 expression in GBM and its correlation with patient survival. GBM cell lines were genetically manipulated using the CRISPR/Cas9 system to deplete CYBC1. The effects of CYBC1 deficiency on cell proliferation, migration, invasion, and cell cycle dynamics were experimentally evaluated. Additionally, the impact of CYBC1 on the expression of NOXA1, a subunit of NADPH oxidase, and downstream signaling pathways such as nuclear factor кB (NF-κB) was explored.
Results
CYBC1 expression was significantly elevated in GBM tissues and correlated with poor patient survival. CYBC1 deficiency in GBM cells resulted in reduced cell viability, migration, and invasion. Mechanistically, CYBC1 positively regulated NOXA1 expression, which in turn enhanced ROS production and activated the ERK·AKT/NF-κB pathways. The suppression of CYBC1 led to decreased ROS levels, reduced phosphorylation of NF-κB, and downregulation of genes involved in epithelial-mesenchymal transition.
Conclusion
CYBC1 is implicated in GBM progression by regulating NOXA1-mediated ROS production and activating the ERK·AKT/NF-κB pathways. This study suggests that CYBC1 could serve as a potential therapeutic target and prognostic marker in GBM, warranting further investigation into its molecular mechanisms and therapeutic potential.

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Breast cancer

Synergistic Activation of LEPR and ADRB2 Induced by Leptin Enhances Reactive Oxygen Specie Generation in Triple-Negative Breast Cancer Cells: Chang Liu, Jing Yu, Yongjun Du, Yu Xie, Xiaofei Song, Chang Liu, Yan Yan, Yue Wang, Junfang Qin; Cancer Res Treat. 2025;57(2):457-477. Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.368

Abstract PDF Supplementary Material PubReader ePub

Purpose
Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear.
Materials and Methods
The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2.
Results
LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects.
Conclusion
This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Citations

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Neural-tumor crosstalk and molecular targeting: mechanisms and therapeutic implications in cancer neuroscience
Tianhui Hou, Huaze Ding, Guofang Huang, Tong Meng, Dianwen Song
Cellular Oncology.2026;[Epub] CrossRef
Metabolic crosstalk among cancer-associated fibroblasts, adipocytes and immune cells as an immunosuppressive tumor microenvironment driver
Tae Hyun Kim, Seong Hun Lim, Hyesung Lee, Young Chan Chae, Do Sik Min
Experimental & Molecular Medicine.2026; 58(2): 366. CrossRef
Marrow leptin-LEPR signaling rewires mitochondrial oxidative metabolism to confer chemoresistance in acute myeloid leukemia
Xinai Liao, Wei Dai, Xiaolin Xu, Danni Cai, Maoqing Tan, Zukai Wang, Yanrong Huang, Diyu Hou, Jingru Liu, Liuhuan Wang, Jin Wang, Xiaoting Wang, Shuxia Zhang, Xinjian Lin, Huifang Huang
Cell Death & Disease.2026;[Epub] CrossRef
Targeting obesity and adipokine signaling in the breast cancer microenvironment for enhanced tumor therapy
Wenhao Li, Jiaman Qu, Weifan Li, Yuan Cao, Rui Xu, Lei Xu
Nanoscale.2026; 18(24): 12603. CrossRef
Dilated Cardiomyopathy May Be Associated With a Novel Mitochondrial tRNASer(AGY) Mutation
Yu Ding, Xuejiao Yu, Jian Xu, Shunrong Zhang, Jianhang Leng, Lars Bertram
Human Mutation.2025;[Epub] CrossRef

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Reactive Oxygen Species Modulator 1 (Romo1) Predicts Poor Outcomes in Advanced Non-small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy: Seung Hyeun Lee, Sue In Choi, Ji Sung Lee, Chul Hwan Kim, Won Jai Jung, Eun Joo Lee, Kyung Hoon Min, Gyu Young Hur, Seung Heon Lee, Sung Yong Lee, Je Hyeong Kim, Sang Yeub Lee, Chol Shin, Jae Jeong Shim, Kyung Ho Kang, Kwang Ho In; Cancer Res Treat. 2017;49(1):141-149. Published online May 18, 2016; DOI: https://doi.org/10.4143/crt.2016.133

Abstract PDF PubReader ePub

Purpose
Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.
Materials and Methods
Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated.
Results
A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology.
Conclusion
Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.

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Prognostic Impact of Reactive Oxygen Species Modulator 1 in Surgically Resected Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinomas
Tae-Woo Kim, Kiyong Na, Junyang Jung, Heejin Lim, Hyewon Seo, Seung Hyeun Lee
Oncology.2024; 102(11): 969. CrossRef
ROMO1 – a potential immunohistochemical prognostic marker for cancer development
Eva Tsoneva, Mariela B. Vasileva-Slaveva, Stoyan G. Kostov, Angel D. Yordanov
Oncologie.2023; 25(6): 753. CrossRef
Serum Reactive Oxygen Species Modulator 1 as a Novel Predictive Biomarker for Resected Lung Adenocarcinoma: A Retrospective Pilot Study
Boksoon Chang, In Kyung Hwang, Seung Hyeun Lee
OncoTargets and Therapy.2021; Volume 14: 5097. CrossRef
Overexpression of Reactive Oxygen Species Modulator 1 Predicts Unfavorable Clinical Outcome in EGFR-Mutant Lung Adenocarcinomas Treated With Targeted Therapy
Won Gun Kwack, Ji-Youn Sung, Seung Hyeun Lee
Frontiers in Oncology.2021;[Epub] CrossRef
Overexpression of reactive oxygen species modulator 1 is associated with advanced grades of bladder cancer
Hadi Ghasemi, Mohammad Amin Amini, Atefeh Pegah, Ebrahim Azizi, Heidar Tayebinia, Shima Khanverdilou, Seyed Habibollah Mousavibahar, Aida Alizamir
Molecular Biology Reports.2020; 47(9): 6497. CrossRef
Reactive Oxygen Species Modulator 1 is Associated with Poor Survival in Patients with Non-Small Cell Lung Cancer After Stereotactic Fractionated Radiosurgery: A Retrospective Pilot Study

Moonkyoo Kong, Ji-Youn Sung, Seung Hyeun Lee
OncoTargets and Therapy.2020; Volume 13: 8173. CrossRef
Reactive oxygen species modulator 1 expression predicts lymph node metastasis and survival in early-stage non-small cell lung cancer
Taehee Kim, Yoon Jin Cha, Ji Hyun Park, Arum Kim, Yong Jun Choi, Hye Jung Park, Jung Weon Lee
PLOS ONE.2020; 15(12): e0239670. CrossRef
Reactive Oxygen Species Modulator 1 (ROMO1), a New Potential Target for Cancer Diagnosis and Treatment
Mohammad Amin Amini, Seyed Saman Talebi, Jamshid Karimi
Chonnam Medical Journal.2019; 55(3): 136. CrossRef
Reactive oxygen species modulator 1 (Romo1) as a novel diagnostic marker for lung cancer-related malignant effusion
Seung Hyeun Lee, Myung Jae Park, Sue In Choi, Eun Joo Lee, Sang Yeub Lee, Kwang Ho In
Medicine.2017; 96(4): e5975. 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

Abstract PDF PubReader ePub

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

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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

Abstract PDF PubReader ePub

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

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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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