Triptolide functions as a potent angiogenesis inhibitor

Ming Fang He, Yi Hsien Huang, Li Wha Wu, Wei Ge, Pang Chui Shaw, Paul Pui Hay But

研究成果: Article同行評審

64 引文 斯高帕斯(Scopus)

摘要

Triptolide is a key anti-inflammatory compound of the Chinese herbal medicine Tripterygium wilfordii Hook. f. (Celastraceae). It also possesses potent antitumor activity. In this study, we show that triptolide is an angiogenesis inhibitor based on various angiogenesis assays. The IC50 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 downregulation of proangiogenic Tie2 and VEGFR-2 expression in human umbilical vein endothelial cell by semiquantitative RT-PCR and western blot analysis. Although Tie2 inhibition appeared to be a later event as compared with VEGFR-2, Tie2 overexpression 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 antitumor action of triptolide is partly via inhibition of tumor angiogenesis by blocking 2 endothelial receptormediated signaling pathways, and triptolide can be a promising antiangiogenic agent.

原文English
頁(從 - 到)266-278
頁數13
期刊International Journal of Cancer
126
發行號1
DOIs
出版狀態Published - 2010 1月 1

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究

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