Abstract
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.
Highlights
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
Since T-96 suppresses the growth of various cancer cells, we investigated if it has anti-cancer effects against CaP cell lines such as DU145 and PC3
We found that T-96 significantly inhibits cell proliferation in a dose- and time-dependent manner (Additional file 1: Figure S1B)
Summary
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. The potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. Cells have evolved a highly protective signal transduction pathway, referred to as unfolded protein response (UPR), to alleviate ER stress by enhancing protein folding ability, reducing protein transduction rate and degrading unfolded and misfolded proteins [9, 10]. If protein folding homeostasis cannot be restored in the ER, UPR initiates an alternative signalling pathway, termed terminal UPR, which eventually promotes apoptosis induced by the toxicity of unfolded/misfolded proteins [9, 10, 14]. The induction of ER stress above a critical threshold by novel compounds and the subsequent activation of the programmed cell death signalling pathway may be an effective strategy for cancer therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
