Mechanism of action of the anti-cancer agent, triptolide

Triptolide, a dipertene triepoxide isolated from the roots of the Chinese herb Tripterygium wilfordii Hook F., is a promising anti-cancer agent. While its role as a promoter of cell death, both in vivo and in vitro, in various cancers is well established, the mechanism by which it induces cell death in cancer cells is not well understood, and has therefore been the subject of intense interest in the past decade. Studies to date have shown that triptolide acts in a pleiotropic fashion, resulting in decrease of HSP70 expression, affecting calcium release, causing lysosomal membrane depolarization, inhibiting NFκB activity, iNOS and Cox-2 expression, as well as acting as a transcription inhibitor and an anti-angiogenesis factor. In this review, we discuss the possible modes of action of triptolide in various cancers, as well as a novel compound derived from triptolide currently being prepared for Phase I clinical trials.