Gambogic acid inhibits angiogenesis through suppressing vascular endothelial growth factor-induced tyrosine phosphorylation of KDR/Flk-1.
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.
Lu
Na
N
Jiangsu Key Laboratory of Carcinogenesis and Intervention (China Pharmaceutical University), Nanjing, PR China.
Yang
Yong
Y
You
Qi-Dong
QD
Ling
Yun
Y
Gao
Ying
Y
Gu
Hong-Yan
HY
Zhao
Li
L
Wang
Xiao-Tang
XT
Guo
Qing-Long
QL
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010766:Phosphorylation / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D044004:Xanthones / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D044004:Xanthones; C059485:matrigel; D014443:Tyrosine; C052659:gambogic acid; D003094:Collagen; D040301:Vascular Endothelial Growth Factor Receptor-2