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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...

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Autores principales: 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
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
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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.
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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
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