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

One of the diverse biological activities of triptolide, a diterpene from Tr ipterygium wilfordii, is its antitumor effect. We recently reported its in vitro cytotoxicity against several cultured tumor cell lines. Limited avail ability of purified fraction has prevented detailed investigation on its an titumor activity. In the present study, we showed by in vitro cytotoxicity assay and in vivo inhibition of tumor growth in hamsters that the triptolid e was also highly effective against cholangiocarcinoma, a highly fatal tumo r predominantly occurring in developing countries. Its ED50 for these hamst er cholangiocarcinoma cell lines was found to be as low as 0.05 mu g/ml. Th e compound was highly potent in the induction of apoptotic death in these t umor cells, DNA fragmentation and disintegrating apoptotic cells could be o bserved within 24 h of exposure to 0.5 mu g/ml triptolide, The compound was tested against the growth of cholangiocarcinoma in a hamster model. A sign ificant growth inhibition (P < 0.05) was noted in triptolide-treated hamste rs (each of the 10 animals received 10 injections for a total of 1.2 mg/ani mal). At the time of sacrifice 1 month after the initial injection, the mea n tumor mass of the treated group was only 20-25% of that of the control gr oup. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.