EVALUATION OF THE MUTAGENIC, CYTOTOXIC, AND ANTITUMOR POTENTIAL OF TRIPTOLIDE, A HIGHLY OXYGENATED DITERPENE ISOLATED FROM TRIPTERYGIUM-WILFORDII

Triptolide, a highly oxygenated diterpene isolated from Tripterygium w ilfordli Hook f. (Celastraceae), has been shown to demonstrate potent antileukemic activity in rodent models at remarkably low treatment dos es. A variety of other physiological responses are known to be mediate d by this compound, including immunosuppressive and antifertility effe cts. We currently report that triptolide was not mutagenic toward Salm onella typhimurium strain TM677, either in the presence or absence of a metabolic activating system. Relatively potent but non-specific cyto toxicity was observed with a panel of cultured mammalian cell lines, a nd modest antitumor activity was observed when an i.p. dose of 25 mu g was administered three times weekly to athymic mice carrying human br east tumors. Treatment regimens involving higher doses of triptolide ( e.g.50 mu g/mouse three times weekly) were lethal. (C) 1997 Elsevier S cience Ireland Ltd.