Mechanisms of cancer cell death induction by triptolide: A comprehensive overview.

ABSTRACT

The need for naturally occurring constituents is driven by the rise in the cancer prevalence and the unpleasant side effects associated with chemotherapeutics. Triptolide, the primary active component of "Tripterygium Wilfordii", has exploited for biological mechanisms and therapeutic potential against various tumors. Based on the recent pre-clinical investigations, triptolide is linked to the induction of death of cancerous cells by triggering cellular apoptosis via inhibiting heat shock protein expression (HSP70), and cyclin dependent kinase (CDKs) by up regulating expression of P21. MKP1, histone methyl transferases and RNA polymerases have all recently identified as potential targets of triptolide in cells. Autophagy, AKT signaling pathway and various pathways involving targeted proteins such as A-disintegrin & metalloprotease-10 (ADAM10), Polycystin-2 (PC-2), dCTP pyro-phosphatase 1 (DCTP1), peroxiredoxin-I (Prx-I), TAK1 binding protein (TAB1), kinase subunit (DNA-PKcs) and the xeroderma-pigmentosum B (XPB or ERCC3) have been exploited. Besides that, triptolide is responsible for enhancing the effectiveness of various chemotherapeutics. In addition, several triptolide moieties, including minnelide and LLDT8, have progressed in investigations on humans for the treatment of cancer. Targeted strategies, such as triptolide conjugation with ligands or triptolide loaded nano-carriers, are efficient techniques to confront toxicities associated with triptolide. We expect and anticipate that advances in near future, regarding combination therapies of triptolide, might be beneficial against cancerous cells.