Journal
CANCER LETTERS
Volume 258, Issue 1, Pages 80-89Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2007.08.015
Keywords
angiogenesis; gambogic acid; VEGF; KDR/Flk-1
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Funding
- NIGMS NIH HHS [S06 GM008205] Funding Source: Medline
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Previous studies revealed that gambogic acid (GA), the major active ingredient of gamboge, a brownish to orange resin exuded from Garcinia hanburryi tree in Southeast Asia, possessed significant anticancer activity both in vitro and in vivo. In this study, we explored the high antiangiogenic activities of GA for the first time. GA inhibits the VEGF-stimulated proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) as well as microvessel sprouting from rat aortic rings in vitro. Moreover, GA inhibits vessel growth in matrigel plugs and CAM in vivo and transplanted tumor in mice. The results also indicated that GA decreases VEGF production of cultured tumor cells and inhibits VEGF-induced tyrosine phosphorylation of KDR/Flk-1. This inhibition of receptor phosphorylation is correlated with a significant decrease in VEGF-triggered phosphorylated forms of ERK, AKT and p38. Taken together, these findings strongly suggest that GA might be a structurally novel angiogenesis inhibitor. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
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