Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux

Abstract Background: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96...

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Autores principales:	Yang,Dong-lin, Zhang,Ya-jun, He,Liu-jun, Hu,Chun-sheng, Gao,Li-xia, Huang,Jiu-hong, Tang,Yan, Luo,Jie, Tang,Dian-yong, Chen,Zhong-zhu
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2021
Materias:	T-96 CaP ER stress Apoptosis Autophagic flux Cisplatin
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602021000100222
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spelling	oai:scielo:S0716-976020210001002222021-09-30Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic fluxYang,Dong-linZhang,Ya-junHe,Liu-junHu,Chun-shengGao,Li-xiaHuang,Jiu-hongTang,YanLuo,JieTang,Dian-yongChen,Zhong-zhu T-96 CaP ER stress Apoptosis Autophagic flux Cisplatin Abstract Background: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. Results: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. Conclusions: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.54 20212021-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602021000100222en10.1186/s40659-021-00350-6
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	T-96 CaP ER stress Apoptosis Autophagic flux Cisplatin
spellingShingle	T-96 CaP ER stress Apoptosis Autophagic flux Cisplatin Yang,Dong-lin Zhang,Ya-jun He,Liu-jun Hu,Chun-sheng Gao,Li-xia Huang,Jiu-hong Tang,Yan Luo,Jie Tang,Dian-yong Chen,Zhong-zhu Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux
description	Abstract Background: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. Results: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. Conclusions: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.
author	Yang,Dong-lin Zhang,Ya-jun He,Liu-jun Hu,Chun-sheng Gao,Li-xia Huang,Jiu-hong Tang,Yan Luo,Jie Tang,Dian-yong Chen,Zhong-zhu
author_facet	Yang,Dong-lin Zhang,Ya-jun He,Liu-jun Hu,Chun-sheng Gao,Li-xia Huang,Jiu-hong Tang,Yan Luo,Jie Tang,Dian-yong Chen,Zhong-zhu
author_sort	Yang,Dong-lin
title	Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux
title_short	Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux
title_full	Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux
title_fullStr	Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux
title_full_unstemmed	Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux
title_sort	demethylzeylasteral (t-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ros-mediated er stress and suppressing autophagic flux
publisher	Sociedad de Biología de Chile
publishDate	2021
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602021000100222
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Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux

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