Abstract
Demethylzeylasteral is one of the extracts of Tripterygium wilfordii Hook F, which plays important roles in multiple biological processes such as inflammation inhibition, as well as immunosuppression. However, anti-cancer function and the underlying mechanisms of demethylzeylasteral in melanoma cells remain unclear. In this study, we demonstrate that demethylzeylasteral has an anti-tumor property in melanoma cells. Demethylzeylasteral not only inhibits cell proliferation through cell cycle arrest at S phase, but also induces cell apoptosis in melanoma cells. MCL1 is an anti-apoptotic protein in BCL2 family, and amplifies frequently in multiple human cancers. MCL1 is also known as a potential contributor for the resistance of BCL2 inhibitors, as well as various chemotherapeutic drugs. MCL1 is, therefore, regarded as a potential target for cancer therapy. Here, for the first time, we unveil that demethylzeylasteral suppresses the expression of MCL1. Interestingly, MCL1 interacts with S phase-related protein CDK2, and thereby inhibits it's ubiquitin-dependent degradation. Together, demethylzeylasteral is a promising anti-tumor compound in melanoma cells. Demethylzeylasteral is also a potential inhibitor of MCL1.