Triptolide functions as a potent angiogenesis inhibitor.

Int J Cancer. 2009 Jun 30; He MF, Huang YH, Wu LW, Ge W, Shaw PC, But PPTriptolide is a key anti-inflammatory compound of the Chinese herbal medicine Tripterygium wilfordii Hook. f. (Celastraceae). It also possesses potent anti-tumor activity. In this study, we show that triptolide is an angiogenesis inhibitor based on various angiogenesis assays. The IC(50) in in vitro assays was 45 nM, which was much lower than the plasma concentrations of triptolide in the rat or human administered with T. wilfordii extracts for treating inflammation. When dosed in vivo, triptolide potently inhibited angiogenesis at 100 nM in Matrigel plug assay. Triptolide at 0.75 mg/kg/day significantly blocked tumor angiogenesis and tumor progression in murine tumorigenesis assay. The underlying mechanism of triptolide correlated with down-regulation of proangiogenic Tie2 and VEGFR-2 expression in HUVEC by semi-quantitative RT-PCR and Western blot analysis. Although Tie2 inhibition appeared to be a later event as compared with VEGFR-2, Tie2 over-expression significantly attenuated the inhibitory effect of triptolide on endothelial proliferation and network formation. By contrast, Tie2 knockdown mimicked the inhibitory effect of triptolide on endothelial network formation. Our findings suggest that anti-tumor action of triptolide is partly via inhibition of tumor angiogenesis by blocking two endothelial receptor-mediated signaling pathways, and triptolide can be a promising anti-angiogenic agent. (c) 2009 UICC.