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Department of Oncology, Georgetown University Medical Center, Washington, DC 20007 [S. Y., J. C., X-M. X., L. W., X-F. P., J. Y., C. B. U., L. Z.], and Key Laboratory of China Education Ministry on Cell Biology and Tumor Cell Engineering, Xiamen University, Fujian, People’s Republic of China 361003 [S. Y., Z. G., L. Z.]

2 To whom requests for reprints should be addressed, at Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, DC 20007. Phone: (202) 687-6397; Fax: (202) 687-7505; E-mail: zhangl{at}georgetown.edu

Triptolide (TPL), a diterpenoid triepoxide purified from the Chinese herb Tripterygium wilfordii Hook F, was tested for its antitumor properties in several model systems. In vitro, TPL inhibited the proliferation and colony formation of tumor cells at extremely low concentrations (2–10 ng/ml) and was more potent than Taxol. Likewise, in vivo, treatment of mice with TPL for 2–3 weeks inhibited the growth of xenografts formed by four different tumor cell lines (B16 melanoma, MDA-435 breast cancer, TSU bladder cancer, and MGC80-3 gastric carcinoma), indicating that TPL has a broad spectrum of activity against tumors that contain both wild-type and mutant forms of p53. In addition, TPL inhibited experimental metastasis of B16F10 cells to the lungs and spleens of mice. The antitumor effect of TPL was comparable or superior with that of conventional antitumor drugs, such as Adriamycin, mitomycin, and cisplatin. Importantly, tumor cells that were resistant to Taxol attributable to the overexpression of the multidrug resistant gene 1 were still sensitive to the effects of TPL. Studies on cultured tumor cells revealed that TPL induced apoptosis and reduced the expression of several molecules that regulate the cell cycle. Taken together, these results suggest that TPL has several attractive features as a new antitumor agent.

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