Triptolide-mediated downregulation of FLIP_S in hepatoma cells occurs at the post-transcriptional level independently of proteasome-mediated pathways.

ABSTRACT: Cellular c-FLIP prevents apoptosis mediated by death receptor through inhibiting activation of caspase-8. Therefore, when c-FLIP is downregulated or eliminated, caspase-8 activation is promoted, and death receptor ligand-induced apoptosis is activated. It was reported that triptolide (TPL) sensitized tumor cells to TNF-α-induced apoptosis by blocking TNF-α-induced activation of NF-κB and transcription of c-IAP1 and c-IAP2. However, the effect of TPL on basal c-FLIP expression was not understood. In this study, we found that the combination of TNF-α and TPL accelerated apoptosis in human hepatocellular carcinoma cells and TNF-α-induced elevated as well as basal level of FLIP_S protein were downregulated by TPL. Additionally, we demonstrated that the basal level of FLIP_S

SUBMITTER: Liu W 

PROVIDER: S-EPMC9617966 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature