期刊
BIOLOGICAL RESEARCH
卷 54, 期 1, 页码 -出版社
SOC BIOLGIA CHILE
DOI: 10.1186/s40659-021-00350-6
关键词
T-96; CaP; ER stress; Apoptosis; Autophagic flux; Cisplatin
类别
资金
- Basic Research and Frontier Program of Chongqing Science and Technology Bureau [cstc2019jcyj-msxmX0727, cstc2020jcyj-msxmX0595, cstc2020jcyj-msxmX0004, cstc2020jcyj-msxmX0733]
- Science and Technology Research Program of Chongqing Municipal Education Commission [KJZD-K20200130, KJQN201901331]
- Scientific Research Foundation of the Chongqing University of Arts and Sciences [2017RBX11, Y2019XY19, Y2020XY14]
In this study, T-96 demonstrated significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest in 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, subsequently activating the extrinsic apoptosis pathway in CaP cells. These findings suggest that T-96-induced ER stress activates the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells.
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.
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