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Triptolide functions as a potent angiogenesis inhibitor
Author(s) -
He MingFang,
Huang YiHsien,
Wu LiWha,
Ge Wei,
Shaw PangChui,
But Paul PuiHay
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24694
Subject(s) - triptolide , angiogenesis , tripterygium wilfordii , angiogenesis inhibitor , pharmacology , human umbilical vein endothelial cell , matrigel , neovascularization , umbilical vein , in vivo , cancer research , chemistry , downregulation and upregulation , endothelial stem cell , medicine , apoptosis , in vitro , biology , biochemistry , pathology , alternative medicine , microbiology and biotechnology , gene
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 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 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 receptor‐mediated signaling pathways, and triptolide can be a promising antiangiogenic agent.