Frontiers in Pharmacology (Oct 2021)
Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation
- Yu Xiang,
- Yu Xiang,
- Xiaying Chen,
- Xiaying Chen,
- Wengang Wang,
- Lijuan Zhai,
- Xueni Sun,
- Xueni Sun,
- Jiao Feng,
- Jiao Feng,
- Ting Duan,
- Ting Duan,
- Mingming Zhang,
- Mingming Zhang,
- Ting Pan,
- Ting Pan,
- Lili Yan,
- Lili Yan,
- Ting Jin,
- Ting Jin,
- Quan Gao,
- Quan Gao,
- Chengyong Wen,
- Chengyong Wen,
- Weirui Ma,
- Weirui Ma,
- Wencheng Liu,
- Wencheng Liu,
- Deqiang Wang,
- Qibiao Wu,
- Tian Xie,
- Tian Xie,
- Tian Xie,
- Xinbing Sui,
- Xinbing Sui,
- Xinbing Sui,
- Xinbing Sui
Affiliations
- Yu Xiang
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Yu Xiang
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Xiaying Chen
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Xiaying Chen
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Wengang Wang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Lijuan Zhai
- Zhejiang Chinese Medical University, Hangzhou, China
- Xueni Sun
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Xueni Sun
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Jiao Feng
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Jiao Feng
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Ting Duan
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Ting Duan
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Mingming Zhang
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Mingming Zhang
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Ting Pan
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Ting Pan
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Lili Yan
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Lili Yan
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Ting Jin
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Ting Jin
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Quan Gao
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Quan Gao
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Chengyong Wen
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Chengyong Wen
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Weirui Ma
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Weirui Ma
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Wencheng Liu
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Wencheng Liu
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Deqiang Wang
- Department of Medical Oncology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China
- Qibiao Wu
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- Tian Xie
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Tian Xie
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Tian Xie
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Xinbing Sui
- School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China
- Xinbing Sui
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China
- Xinbing Sui
- Department of Medical Oncology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China
- Xinbing Sui
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- DOI
- https://doi.org/10.3389/fphar.2021.775506
- Journal volume & issue
-
Vol. 12
Abstract
Erianin, a natural product derived from Dendrobium chrysotoxum Lindl, has been proved to play antitumor activity in various cancers. However, the effects and molecular mechanisms of erianin in bladder cancer cells remain unexplored. In this study, we found that erianin triggered cell death and cell cycle arrest in bladder cancer cells. Then we demonstrated that erianin could promote the accumulation of lethal lipid-based reactive oxygen species (ROS) and the depletion of glutathione (GSH), suggesting the induction of ferroptosis. In the further study, the ferroptosis inhibitor deferoxamine (DFO), N-Acetylcysteine (NAC) and GSH but not necrostatin-1, CQ or Z-VAD-FMK rescued erianin-caused cell death, showing ferroptosis played a major role in erianin-caused cell death. In vivo, we also showed that erianin suppressed the tumor growth by inducing ferroptosis. Mechanistically, we demonstrated that nuclear factor E2-related factor 2 (NRF2) inactivation was a key determinant of ferroptosis caused by erianin. In bladder cancer cells, the compound tert-butylhydro-quinone (TBHQ), an activator of NRF2, suppressed erianin-induced ferroptosis. Whereas, NRF2 inhibition used shRNA augmented the ferroptosis response induced by erianin treatment. In conclusion, our data provide the first evidence that erianin can initiate ferroptosis-like cell death and lipid peroxidation in bladder cancer, which will hopefully become a promising anticancer compound for the treatment of bladder cancer.
Keywords
