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

Biological Research

Dian-yong Tang¹  Li-xia Gao¹  Ya-jun Zhang¹  Liu-jun He¹  Yan Tang¹  Chun-sheng Hu¹  Jie Luo¹  Zhong-zhu Chen¹  Dong-lin Yang²  Jiu-hong Huang² 

[1] College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing University of Arts and Sciences, 402160, Chongqing, China;College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing University of Arts and Sciences, 402160, Chongqing, China;College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, 400715, Chongqing, China;

关键词: T-96;    CaP;    ER stress;    Apoptosis;    Autophagic flux;    Cisplatin;   

DOI  :  10.1186/s40659-021-00350-6

来源: Springer

【 摘 要 】

BackgroundDemethylzeylasteral (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.ResultsIn 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.ConclusionsTaken 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.

【 授权许可】

CC BY