Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress
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...
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doaj-116a8561198248c09f695542bf4c46602021-07-23T13:28:39ZengMDPI AGAntioxidants2076-39212021-06-01101063106310.3390/antiox10071063Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative StressTsu-Ming Chien0Kuang-Han Wu1Ya-Ting Chuang2Yun-Chiao Yeh3Hui-Ru Wang4Bi-Wen Yeh5Chia-Hung Yen6Tzu-Jung Yu7Wen-Jeng Wu8Hsueh-Wei Chang9Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, TaiwanWithaferin 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 (<i>NFE2L2</i>), catalase (<i>CAT</i>), superoxide dismutase 1 (<i>SOD1</i>), thioredoxin (<i>TXN</i>), glutathione-disulfide reductase (<i>GSR</i>), quinone dehydrogenase 1 (<i>NQO1</i>), and heme oxygenase 1 (<i>HMOX1</i>), are overexpressed in J82 cells. In addition, WFA causes DNA strand breaks and oxidative DNA damages. Moreover, the ROS scavenger <i>N</i>-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.https://www.mdpi.com/2076-3921/10/7/1063Withaferin Abladder cancerDNA damageapoptosisoxidative stress |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tsu-Ming Chien Kuang-Han Wu Ya-Ting Chuang Yun-Chiao Yeh Hui-Ru Wang Bi-Wen Yeh Chia-Hung Yen Tzu-Jung Yu Wen-Jeng Wu Hsueh-Wei Chang |
spellingShingle |
Tsu-Ming Chien Kuang-Han Wu Ya-Ting Chuang Yun-Chiao Yeh Hui-Ru Wang Bi-Wen Yeh Chia-Hung Yen Tzu-Jung Yu Wen-Jeng Wu Hsueh-Wei Chang Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress Antioxidants Withaferin A bladder cancer DNA damage apoptosis oxidative stress |
author_facet |
Tsu-Ming Chien Kuang-Han Wu Ya-Ting Chuang Yun-Chiao Yeh Hui-Ru Wang Bi-Wen Yeh Chia-Hung Yen Tzu-Jung Yu Wen-Jeng Wu Hsueh-Wei Chang |
author_sort |
Tsu-Ming Chien |
title |
Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress |
title_short |
Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress |
title_full |
Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress |
title_fullStr |
Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress |
title_full_unstemmed |
Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress |
title_sort |
withaferin a triggers apoptosis and dna damage in bladder cancer j82 cells through oxidative stress |
publisher |
MDPI AG |
series |
Antioxidants |
issn |
2076-3921 |
publishDate |
2021-06-01 |
description |
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 (<i>NFE2L2</i>), catalase (<i>CAT</i>), superoxide dismutase 1 (<i>SOD1</i>), thioredoxin (<i>TXN</i>), glutathione-disulfide reductase (<i>GSR</i>), quinone dehydrogenase 1 (<i>NQO1</i>), and heme oxygenase 1 (<i>HMOX1</i>), are overexpressed in J82 cells. In addition, WFA causes DNA strand breaks and oxidative DNA damages. Moreover, the ROS scavenger <i>N</i>-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. |
topic |
Withaferin A bladder cancer DNA damage apoptosis oxidative stress |
url |
https://www.mdpi.com/2076-3921/10/7/1063 |
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