withanolide E

Withanolide E is a natural steroidal lactone isolated from the plant *Physalis peruviana* (Cape gooseberry). It has been identified as a potent sensitizer of various human cancer cell lines, particularly renal cell carcinoma and melanoma, to apoptosis induced by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and the TLR3 ligand poly(I:C). Its mechanism of action involves the reduction of cellular levels of the antiapoptotic protein c-FLIP (both long and short isoforms) and the enhancement of caspase-8 activation at the death-inducing signaling complex (DISC). Unlike proteasome inhibitors such as bortezomib, withanolide E does not inhibit the proteasome, and its sensitizing effects are dependent on cellular redox changes, as they can be blocked by antioxidants like n-acetyl cysteine. It belongs to the 17-beta-hydroxywithanolide class of compounds and serves as a scaffold for the development of more potent apoptosis-inducing agents.

Other names

WE