Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters

Abstract

One of the diverse biological activities of triptolide, a diterpene from Tripterygium wilfordii, is its antitumor effect. We recently reported its in vitro cytotoxicity against several cultured tumor cell lines. Limited availability of purified fraction has prevented detailed investigation on its antitumor activity. In the present study, we showed by in vitro cytotoxicity assay and in vivo inhibition of tumor growth in hamsters that the triptolide was also highly effective against cholangiocarcinoma, a highly fatal tumor predominantly occurring in developing countries. Its ED50 for these hamster cholangiocarcinoma cell lines was found to be as low as 0.05 microg/ml. The compound was highly potent in the induction of apoptotic death in these tumor cells. DNA fragmentation and disintegrating apoptotic cells could be observed within 24 h of exposure to 0.5 microg/ml triptolide. The compound was tested against the growth of cholangiocarcinoma in a hamster model. A significant growth inhibition (P < 0.05) was noted in triptolide-treated hamsters (each of the 10 animals received 10 injections for a total of 1.2 mg/animal). At the time of sacrifice 1 month after the initial injection, the mean tumor mass of the treated group was only 20-25% of that of the control group.