Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis.
Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize mul...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3554754?pdf=render |
| _version_ | 1818587264138084352 |
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| author | Yong Wang He Wang Wei Zhang Chen Shao Peng Xu Chang Hong Shi Jian Guo Shi Yu Mei Li Qiang Fu Wei Xue Yong Hua Lei Jing Yu Gao Juan Ying Wang Xiao Ping Gao Jin Qing Li Jian Lin Yuan Yun Tao Zhang |
| author_facet | Yong Wang He Wang Wei Zhang Chen Shao Peng Xu Chang Hong Shi Jian Guo Shi Yu Mei Li Qiang Fu Wei Xue Yong Hua Lei Jing Yu Gao Juan Ying Wang Xiao Ping Gao Jin Qing Li Jian Lin Yuan Yun Tao Zhang |
| author_sort | Yong Wang |
| collection | DOAJ |
| description | Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-κB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-κB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy. |
| first_indexed | 2024-12-16T09:06:05Z |
| format | Article |
| id | doaj.art-96e898196a6849fc800d9dc112722a4e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T09:06:05Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-96e898196a6849fc800d9dc112722a4e2022-12-21T22:37:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5017510.1371/journal.pone.0050175Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis.Yong WangHe WangWei ZhangChen ShaoPeng XuChang Hong ShiJian Guo ShiYu Mei LiQiang FuWei XueYong Hua LeiJing Yu GaoJuan Ying WangXiao Ping GaoJin Qing LiJian Lin YuanYun Tao ZhangBladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-κB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-κB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy.http://europepmc.org/articles/PMC3554754?pdf=render |
| spellingShingle | Yong Wang He Wang Wei Zhang Chen Shao Peng Xu Chang Hong Shi Jian Guo Shi Yu Mei Li Qiang Fu Wei Xue Yong Hua Lei Jing Yu Gao Juan Ying Wang Xiao Ping Gao Jin Qing Li Jian Lin Yuan Yun Tao Zhang Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis. PLoS ONE |
| title | Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis. |
| title_full | Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis. |
| title_fullStr | Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis. |
| title_full_unstemmed | Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis. |
| title_short | Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis. |
| title_sort | genistein sensitizes bladder cancer cells to hcpt treatment in vitro and in vivo via atm nf κb ikk pathway induced apoptosis |
| url | http://europepmc.org/articles/PMC3554754?pdf=render |
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