Cargando…
Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation
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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585785/ https://www.ncbi.nlm.nih.gov/pubmed/34776986 http://dx.doi.org/10.3389/fphar.2021.775506 |
_version_ | 1784597755532935168 |
---|---|
author | Xiang, Yu Chen, Xiaying Wang, Wengang Zhai, Lijuan Sun, Xueni Feng, Jiao Duan, Ting Zhang, Mingming Pan, Ting Yan, Lili Jin, Ting Gao, Quan Wen, Chengyong Ma, Weirui Liu, Wencheng Wang, Deqiang Wu, Qibiao Xie, Tian Sui, Xinbing |
author_facet | Xiang, Yu Chen, Xiaying Wang, Wengang Zhai, Lijuan Sun, Xueni Feng, Jiao Duan, Ting Zhang, Mingming Pan, Ting Yan, Lili Jin, Ting Gao, Quan Wen, Chengyong Ma, Weirui Liu, Wencheng Wang, Deqiang Wu, Qibiao Xie, Tian Sui, Xinbing |
author_sort | Xiang, Yu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8585785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85857852021-11-13 Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation Xiang, Yu Chen, Xiaying Wang, Wengang Zhai, Lijuan Sun, Xueni Feng, Jiao Duan, Ting Zhang, Mingming Pan, Ting Yan, Lili Jin, Ting Gao, Quan Wen, Chengyong Ma, Weirui Liu, Wencheng Wang, Deqiang Wu, Qibiao Xie, Tian Sui, Xinbing Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-10-29 /pmc/articles/PMC8585785/ /pubmed/34776986 http://dx.doi.org/10.3389/fphar.2021.775506 Text en Copyright © 2021 Xiang, Chen, Wang, Zhai, Sun, Feng, Duan, Zhang, Pan, Yan, Jin, Gao, Wen, Ma, Liu, Wang, Wu, Xie and Sui. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Xiang, Yu Chen, Xiaying Wang, Wengang Zhai, Lijuan Sun, Xueni Feng, Jiao Duan, Ting Zhang, Mingming Pan, Ting Yan, Lili Jin, Ting Gao, Quan Wen, Chengyong Ma, Weirui Liu, Wencheng Wang, Deqiang Wu, Qibiao Xie, Tian Sui, Xinbing Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation |
title | Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation |
title_full | Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation |
title_fullStr | Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation |
title_full_unstemmed | Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation |
title_short | Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation |
title_sort | natural product erianin inhibits bladder cancer cell growth by inducing ferroptosis via nrf2 inactivation |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585785/ https://www.ncbi.nlm.nih.gov/pubmed/34776986 http://dx.doi.org/10.3389/fphar.2021.775506 |
work_keys_str_mv | AT xiangyu naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT chenxiaying naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT wangwengang naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT zhailijuan naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT sunxueni naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT fengjiao naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT duanting naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT zhangmingming naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT panting naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT yanlili naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT jinting naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT gaoquan naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT wenchengyong naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT maweirui naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT liuwencheng naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT wangdeqiang naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT wuqibiao naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT xietian naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation AT suixinbing naturalproducterianininhibitsbladdercancercellgrowthbyinducingferroptosisvianrf2inactivation |