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Article

Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress

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Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
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Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Authors to whom correspondence should be addressed.
Academic Editors: Neven Zarkovic and Suzana Borović Šunjić
Antioxidants 2021, 10(7), 1063; https://doi.org/10.3390/antiox10071063
Received: 7 June 2021 / Revised: 25 June 2021 / Accepted: 29 June 2021 / Published: 30 June 2021
(This article belongs to the Special Issue Anticancer Antioxidants)
Withaferin A (WFA), the Indian ginseng bioactive compound, exhibits an antiproliferation effect on several kinds of cancer, but it was rarely reported in bladder cancer cells. This study aims to assess the anticancer effect and mechanism of WFA in bladder cancer cells. WFA shows antiproliferation to bladder cancer J82 cells based on the finding of the MTS assay. WFA disturbs cell cycle progression associated with subG1 accumulation in J82 cells. Furthermore, WFA triggers apoptosis as determined by flow cytometry assays using annexin V/7-aminoactinomycin D and pancaspase detection. Western blotting also supports WFA-induced apoptosis by increasing cleavage of caspases 3, 8, and 9 and poly ADP-ribose polymerase. Mechanistically, WFA triggers oxidative stress-association changes, such as the generation of reactive oxygen species and mitochondrial superoxide and diminishment of the mitochondrial membrane potential, in J82 cells. In response to oxidative stresses, mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), superoxide dismutase 1 (SOD1), thioredoxin (TXN), glutathione-disulfide reductase (GSR), quinone dehydrogenase 1 (NQO1), and heme oxygenase 1 (HMOX1), are overexpressed in J82 cells. In addition, WFA causes DNA strand breaks and oxidative DNA damages. Moreover, the ROS scavenger N-acetylcysteine reverts all tested WFA-modulating effects. In conclusion, WFA possesses anti-bladder cancer effects by inducing antiproliferation, apoptosis, and DNA damage in an oxidative stress-dependent manner. View Full-Text
Keywords: Withaferin A; bladder cancer; DNA damage; apoptosis; oxidative stress Withaferin A; bladder cancer; DNA damage; apoptosis; oxidative stress
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MDPI and ACS Style

Chien, T.-M.; Wu, K.-H.; Chuang, Y.-T.; Yeh, Y.-C.; Wang, H.-R.; Yeh, B.-W.; Yen, C.-H.; Yu, T.-J.; Wu, W.-J.; Chang, H.-W. Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress. Antioxidants 2021, 10, 1063. https://doi.org/10.3390/antiox10071063

AMA Style

Chien T-M, Wu K-H, Chuang Y-T, Yeh Y-C, Wang H-R, Yeh B-W, Yen C-H, Yu T-J, Wu W-J, Chang H-W. Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress. Antioxidants. 2021; 10(7):1063. https://doi.org/10.3390/antiox10071063

Chicago/Turabian Style

Chien, Tsu-Ming, Kuang-Han Wu, Ya-Ting Chuang, Yun-Chiao Yeh, Hui-Ru Wang, Bi-Wen Yeh, Chia-Hung Yen, Tzu-Jung Yu, Wen-Jeng Wu, and Hsueh-Wei Chang. 2021. "Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress" Antioxidants 10, no. 7: 1063. https://doi.org/10.3390/antiox10071063

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