Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4

Kewen Zheng

doi:doi:10.11648/j.ijcu.20250901.23

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Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4

Kewen Zheng^*

Published in International Journal of Clinical Urology (Volume 9, Issue 1)

Received: 8 April 2025 Accepted: 16 April 2025 Published: 19 May 2025

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Abstract

Background: Bladder cancer is one of the most common malignancies globally, with high recurrence rates and limited therapeutic efficacy in advanced stages. Current treatments, including chemotherapy and immunotherapy, often face challenges such as drug resistance and severe side effects. Therefore, identifying novel therapeutic agents with improved efficacy and safety profiles is critical. Arsenic trioxide (ATO), a compound with established anti-cancer properties in other malignancies, has shown potential in modulating oxidative stress pathways, but its effects on bladder cancer remain underexplored. Objective: This study aims to investigate the inhibitory effects of ATO on the proliferation of bladder cancer T24 cells and elucidate the underlying molecular mechanisms, particularly focusing on the glutathione peroxidase 4 (GPX4)-mediated oxidative stress response. Main Ideas: The anti-proliferative effects of ATO were evaluated using the Cell Counting Kit-8 (CCK-8) assay, revealing a significant dose-dependent inhibition of T24 cell viability after 48 hours of treatment, with an IC50 value of 0.289 mg/L. Western Blot analysis demonstrated that ATO markedly reduced GPX4 expression, a key regulator of ferroptosis and oxidative stress. These findings suggest that ATO suppresses bladder cancer cell growth by disrupting redox homeostasis, potentially through GPX4 downregulation. The study provides mechanistic evidence linking ATO’s anti-cancer effects to oxidative stress modulation in bladder cancer cells. Conclusion: Our results highlight ATO as a promising therapeutic candidate for bladder cancer, acting via GPX4-mediated oxidative stress pathways. These findings contribute to the growing body of research on redox-targeted therapies and warrant further investigation into ATO’s clinical applicability, either as a monotherapy or in combination with existing treatments. Future studies should validate these results in vivo and explore synergistic strategies to enhance therapeutic outcomes. This work underscores the potential of ATO in developing novel, targeted approaches for bladder cancer management.

Published in	International Journal of Clinical Urology (Volume 9, Issue 1)
DOI	10.11648/j.ijcu.20250901.23
Page(s)	80-84
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

Bladder Cancer, Proliferation, Arsenic Trioxide, Glutathione Peroxidase 4

References

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[2]	Rahman MA, Hassler C. Is arsenic biotransformation a detoxification mechanism for microorganisms? Aquat Toxicol. 146:212-9. https://doi.org/10.1016/j.aquatox.2013.11.009
[3]	Zhang X, Sui S, Wang L, et al. Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin. J Cell Physiol. 2020; 235(4): 3425-3437. https://doi.org/10.1002/jcp.29232
[4]	Ran Q, Liang H, Gu M, et al. Transgenic mice overexpressing glutathione peroxidase 4 are protected against oxidative stress-induced apoptosis. J Biol Chem. 2004; 279(53): 55137-46. https://doi.org/10.1074/jbc.M410387200
[5]	Li BT, Yu C, Xu Y, Liu SB, Fan HY, Pan WW. TET1 inhibits cell proliferation by inducing RASSF5 expression. Oncotarget. 2017; 8(49): 86395-86409. Published 2017 Oct 17. https://doi.org/10.18632/oncotarget.21189
[6]	Huang K, Chen C, Zhang J, et al. Efficient Arsenic Methylation and Volatilization Mediated by a Novel Bacterium from an Arsenic-Contaminated Paddy Soil. Environ Sci Technol. 2016; 50(12): 6389-96. https://doi.org/10.1021/acs.est.6b01974
[7]	Tran P, Rama Sai P, Prasad C, Do H, Parsa C. Mixed neuroendocrine-nonneuroendocrine epithelial neoplasm of muscle invasive bladder cancer: a clinicopathologic case study. J Surg Case Rep. 2024; 2024(10): rjae612. Published 2024 Oct. https://doi.org/10.1093/jscr/rjae612
[8]	Patel VG, Oh WK, Galsky MD. Treatment of muscle-invasive and advanced bladder cancer in 2020. CA Cancer J Clin. 2020 Sep; 70(5): 404-423. https://doi.org/10.3322/caac.21631
[9]	Tran L, Xiao JF, Agarwal N, Duex JE, Theodorescu D. Advances in bladder cancer biology and therapy. Nat Rev Cancer. 2021 Feb; 21(2): 104-121. https://doi.org/10.1038/s41568-020-00313-1
[10]	Chen Z, Liu F, Ren Q, et al. Suppression of ABCG2 inhibits cancer cell proliferation. Int J Cancer. 2010; 126(4): 841-51. https://doi.org/10.1002/ijc.24796
[11]	Yoo SE, Chen L, Na R, et al. Gpx4 ablation in adult mice results in a lethal phenotype accompanied by neuronal loss in brain. Free Radic Biol Med. 2012; 52(9): 1820-7. https://doi.org/10.1016/j.freeradbiomed.2012.02.043
[12]	Liang D, Feng Y, Zandkarimi F, Wang H, Zhang Z, Kim J, Cai Y, Gu W, Stockwell BR, Jiang X. Ferroptosis surveillance independent of GPX4 and differentially regulated by sex hormones. Cell. 2023 Jun 22; 186(13): 2748-2764.e22. https://doi.org/10.1016/j.cell.2023.05.003
[13]	Liu XK, Liu HB, Kong CZ. [Effects of gene Livin transfection affect on the apoptosis in bladder carcinoma cells]. Zhonghua Yi Xue Za Zhi. 2008; 88(12): 853-5. https://pubmed.ncbi.nlm.nih.gov/18756993/
[14]	Meng S, Zhu Y, Li JF, et al. Apigenin inhibits renal cell carcinoma cell proliferation. Oncotarget. 2017; 8(12): 19834-19842. https://doi.org/10.18632/oncotarget.15771

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APA Style

Zheng, K. (2025). Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4. International Journal of Clinical Urology, 9(1), 80-84. https://doi.org/10.11648/j.ijcu.20250901.23

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ACS Style

Zheng, K. Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4. Int. J. Clin. Urol. 2025, 9(1), 80-84. doi: 10.11648/j.ijcu.20250901.23

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AMA Style

Zheng K. Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4. Int J Clin Urol. 2025;9(1):80-84. doi: 10.11648/j.ijcu.20250901.23

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@article{10.11648/j.ijcu.20250901.23,
  author = {Kewen Zheng},
  title = {Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4
},
  journal = {International Journal of Clinical Urology},
  volume = {9},
  number = {1},
  pages = {80-84},
  doi = {10.11648/j.ijcu.20250901.23},
  url = {https://doi.org/10.11648/j.ijcu.20250901.23},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcu.20250901.23},
  abstract = {Background: Bladder cancer is one of the most common malignancies globally, with high recurrence rates and limited therapeutic efficacy in advanced stages. Current treatments, including chemotherapy and immunotherapy, often face challenges such as drug resistance and severe side effects. Therefore, identifying novel therapeutic agents with improved efficacy and safety profiles is critical. Arsenic trioxide (ATO), a compound with established anti-cancer properties in other malignancies, has shown potential in modulating oxidative stress pathways, but its effects on bladder cancer remain underexplored. Objective: This study aims to investigate the inhibitory effects of ATO on the proliferation of bladder cancer T24 cells and elucidate the underlying molecular mechanisms, particularly focusing on the glutathione peroxidase 4 (GPX4)-mediated oxidative stress response. Main Ideas: The anti-proliferative effects of ATO were evaluated using the Cell Counting Kit-8 (CCK-8) assay, revealing a significant dose-dependent inhibition of T24 cell viability after 48 hours of treatment, with an IC50 value of 0.289 mg/L. Western Blot analysis demonstrated that ATO markedly reduced GPX4 expression, a key regulator of ferroptosis and oxidative stress. These findings suggest that ATO suppresses bladder cancer cell growth by disrupting redox homeostasis, potentially through GPX4 downregulation. The study provides mechanistic evidence linking ATO’s anti-cancer effects to oxidative stress modulation in bladder cancer cells. Conclusion: Our results highlight ATO as a promising therapeutic candidate for bladder cancer, acting via GPX4-mediated oxidative stress pathways. These findings contribute to the growing body of research on redox-targeted therapies and warrant further investigation into ATO’s clinical applicability, either as a monotherapy or in combination with existing treatments. Future studies should validate these results in vivo and explore synergistic strategies to enhance therapeutic outcomes. This work underscores the potential of ATO in developing novel, targeted approaches for bladder cancer management.
},
 year = {2025}
}

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TY  - JOUR
T1  - Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4

AU  - Kewen Zheng
Y1  - 2025/05/19
PY  - 2025
N1  - https://doi.org/10.11648/j.ijcu.20250901.23
DO  - 10.11648/j.ijcu.20250901.23
T2  - International Journal of Clinical Urology
JF  - International Journal of Clinical Urology
JO  - International Journal of Clinical Urology
SP  - 80
EP  - 84
PB  - Science Publishing Group
SN  - 2640-1355
UR  - https://doi.org/10.11648/j.ijcu.20250901.23
AB  - Background: Bladder cancer is one of the most common malignancies globally, with high recurrence rates and limited therapeutic efficacy in advanced stages. Current treatments, including chemotherapy and immunotherapy, often face challenges such as drug resistance and severe side effects. Therefore, identifying novel therapeutic agents with improved efficacy and safety profiles is critical. Arsenic trioxide (ATO), a compound with established anti-cancer properties in other malignancies, has shown potential in modulating oxidative stress pathways, but its effects on bladder cancer remain underexplored. Objective: This study aims to investigate the inhibitory effects of ATO on the proliferation of bladder cancer T24 cells and elucidate the underlying molecular mechanisms, particularly focusing on the glutathione peroxidase 4 (GPX4)-mediated oxidative stress response. Main Ideas: The anti-proliferative effects of ATO were evaluated using the Cell Counting Kit-8 (CCK-8) assay, revealing a significant dose-dependent inhibition of T24 cell viability after 48 hours of treatment, with an IC50 value of 0.289 mg/L. Western Blot analysis demonstrated that ATO markedly reduced GPX4 expression, a key regulator of ferroptosis and oxidative stress. These findings suggest that ATO suppresses bladder cancer cell growth by disrupting redox homeostasis, potentially through GPX4 downregulation. The study provides mechanistic evidence linking ATO’s anti-cancer effects to oxidative stress modulation in bladder cancer cells. Conclusion: Our results highlight ATO as a promising therapeutic candidate for bladder cancer, acting via GPX4-mediated oxidative stress pathways. These findings contribute to the growing body of research on redox-targeted therapies and warrant further investigation into ATO’s clinical applicability, either as a monotherapy or in combination with existing treatments. Future studies should validate these results in vivo and explore synergistic strategies to enhance therapeutic outcomes. This work underscores the potential of ATO in developing novel, targeted approaches for bladder cancer management.

VL  - 9
IS  - 1
ER  -

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Author Information

Kewen Zheng

Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, The First Clinical College of Wenzhou Medical University, Wenzhou City, R. P. China

Contact Email

http://orcid.org/0000-0002-4475-2998

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APA Style

Zheng, K. (2025). Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4. International Journal of Clinical Urology, 9(1), 80-84. https://doi.org/10.11648/j.ijcu.20250901.23

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ACS Style

Zheng, K. Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4. Int. J. Clin. Urol. 2025, 9(1), 80-84. doi: 10.11648/j.ijcu.20250901.23

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AMA Style

Zheng K. Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4. Int J Clin Urol. 2025;9(1):80-84. doi: 10.11648/j.ijcu.20250901.23

Copy | Download

@article{10.11648/j.ijcu.20250901.23,
  author = {Kewen Zheng},
  title = {Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4
},
  journal = {International Journal of Clinical Urology},
  volume = {9},
  number = {1},
  pages = {80-84},
  doi = {10.11648/j.ijcu.20250901.23},
  url = {https://doi.org/10.11648/j.ijcu.20250901.23},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcu.20250901.23},
  abstract = {Background: Bladder cancer is one of the most common malignancies globally, with high recurrence rates and limited therapeutic efficacy in advanced stages. Current treatments, including chemotherapy and immunotherapy, often face challenges such as drug resistance and severe side effects. Therefore, identifying novel therapeutic agents with improved efficacy and safety profiles is critical. Arsenic trioxide (ATO), a compound with established anti-cancer properties in other malignancies, has shown potential in modulating oxidative stress pathways, but its effects on bladder cancer remain underexplored. Objective: This study aims to investigate the inhibitory effects of ATO on the proliferation of bladder cancer T24 cells and elucidate the underlying molecular mechanisms, particularly focusing on the glutathione peroxidase 4 (GPX4)-mediated oxidative stress response. Main Ideas: The anti-proliferative effects of ATO were evaluated using the Cell Counting Kit-8 (CCK-8) assay, revealing a significant dose-dependent inhibition of T24 cell viability after 48 hours of treatment, with an IC50 value of 0.289 mg/L. Western Blot analysis demonstrated that ATO markedly reduced GPX4 expression, a key regulator of ferroptosis and oxidative stress. These findings suggest that ATO suppresses bladder cancer cell growth by disrupting redox homeostasis, potentially through GPX4 downregulation. The study provides mechanistic evidence linking ATO’s anti-cancer effects to oxidative stress modulation in bladder cancer cells. Conclusion: Our results highlight ATO as a promising therapeutic candidate for bladder cancer, acting via GPX4-mediated oxidative stress pathways. These findings contribute to the growing body of research on redox-targeted therapies and warrant further investigation into ATO’s clinical applicability, either as a monotherapy or in combination with existing treatments. Future studies should validate these results in vivo and explore synergistic strategies to enhance therapeutic outcomes. This work underscores the potential of ATO in developing novel, targeted approaches for bladder cancer management.
},
 year = {2025}
}

Copy | Download

TY  - JOUR
T1  - Exploration of the Mechanism of Arsenic Trioxide Inhibits the Proliferation of Bladder Cancer T24 Cells by Inhibiting Glutathione Peroxidase 4

AU  - Kewen Zheng
Y1  - 2025/05/19
PY  - 2025
N1  - https://doi.org/10.11648/j.ijcu.20250901.23
DO  - 10.11648/j.ijcu.20250901.23
T2  - International Journal of Clinical Urology
JF  - International Journal of Clinical Urology
JO  - International Journal of Clinical Urology
SP  - 80
EP  - 84
PB  - Science Publishing Group
SN  - 2640-1355
UR  - https://doi.org/10.11648/j.ijcu.20250901.23
AB  - Background: Bladder cancer is one of the most common malignancies globally, with high recurrence rates and limited therapeutic efficacy in advanced stages. Current treatments, including chemotherapy and immunotherapy, often face challenges such as drug resistance and severe side effects. Therefore, identifying novel therapeutic agents with improved efficacy and safety profiles is critical. Arsenic trioxide (ATO), a compound with established anti-cancer properties in other malignancies, has shown potential in modulating oxidative stress pathways, but its effects on bladder cancer remain underexplored. Objective: This study aims to investigate the inhibitory effects of ATO on the proliferation of bladder cancer T24 cells and elucidate the underlying molecular mechanisms, particularly focusing on the glutathione peroxidase 4 (GPX4)-mediated oxidative stress response. Main Ideas: The anti-proliferative effects of ATO were evaluated using the Cell Counting Kit-8 (CCK-8) assay, revealing a significant dose-dependent inhibition of T24 cell viability after 48 hours of treatment, with an IC50 value of 0.289 mg/L. Western Blot analysis demonstrated that ATO markedly reduced GPX4 expression, a key regulator of ferroptosis and oxidative stress. These findings suggest that ATO suppresses bladder cancer cell growth by disrupting redox homeostasis, potentially through GPX4 downregulation. The study provides mechanistic evidence linking ATO’s anti-cancer effects to oxidative stress modulation in bladder cancer cells. Conclusion: Our results highlight ATO as a promising therapeutic candidate for bladder cancer, acting via GPX4-mediated oxidative stress pathways. These findings contribute to the growing body of research on redox-targeted therapies and warrant further investigation into ATO’s clinical applicability, either as a monotherapy or in combination with existing treatments. Future studies should validate these results in vivo and explore synergistic strategies to enhance therapeutic outcomes. This work underscores the potential of ATO in developing novel, targeted approaches for bladder cancer management.

VL  - 9
IS  - 1
ER  -

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