Journal
BIOCHEMICAL PHARMACOLOGY
Volume 72, Issue 4, Pages 437-445Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2006.04.034
Keywords
anti-angiogenesis; ginsenosides; Rg(3); HUVEC
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Aberrant angiogenesis is an essential step for the progression of solid tumors. Thus anti-angiogenic therapy is one of the most promising approaches to control tumor growth. In this study, we examined the ability of 20(R)-ginsenoside Rg(3) (Rg(3)) one of the active compounds present in ginseng root, to interfere with the various steps of angiogenesis. Rg(3) Was found to inhibit the proliferation of human umbilical Vein endothelial cells (HUVEC) with an IC50 of 10 nM in Trypan blue exclusion assay. Rg(3) (1-10 (3) nM) also dose dependently suppressed the capillary tube formation of HUVEC on the Matrigel in the presence or absence of 20 ng/ml vascular endothelial growth factor (VEGF). The VEGF-induced chemoinvasion of HUVEC and ex vivo microvascular sprouting in rat aortic ring assay were both significantly attenuated by Rg(3). In addition, Rg(3) (150 and 600 nM) remarkably abolished the basic fibroblast growth factor (bFGF)-induced angiogenesis in an in vivo Matrigel plug assay. The Matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, which play an important role in the degradation of basement membrane in angiogenesis and tumor metastasis present in the culture supernatant of Rg(3)-treated aortic ring culture were found to decrease in their gelatinolytic activities. Taken together, these data underpin the anti-tumor property of Rg(3) through its angiosuppressive activity. (c) 2006 Published by Elsevier Inc.
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