Arenobufagin, a bufadienolide compound from toad venom, inhibits VEGF-mediated angiogenesis through suppression of VEGFR-2 signaling pathway.
Angiogenesis is crucial for carcinogenesis and other angiogenic processes. Arenobufagin, one of the major components of toad venom, is a traditional Chinese medicine used for cancer therapy. It inhibits cell growth in several cancer cell lines. However, little is known about arenobufagin's anti-angiogenic activity. In this study, we showed that arenobufagin inhibited vascular endothelial growth factor (VEGF)-induced viability, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in vitro. Arenobufagin also suppressed sprouting formation from VEGF-treated aortic rings in an ex vivo model. Furthermore, we found that arenobufagin blocked angiogenesis in a matrigel plugs assay. Computer simulations suggested that arenobufagin interacted with the ATP-binding sites of VEGFR-2 by docking. In addition, arenobufagin inhibited VEGF-induced VEGFR-2 auto-phosphorylation and suppressed the activity of VEGFR-2-mediated signaling cascades. Taken together, our findings demonstrate that arenobufagin is a specific inhibitor of VEGF-mediated angiogenesis.
Institute of Traditional Chinese Medicine and Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, PR China.
Manmei
M
Li
Shuai
S
Wu
Zhong
Z
Liu
Wei
W
Zhang
Jing
J
Xu
Ying
Y
Wang
Junshan
J
Liu
Dongmei
D
Zhang
Haiyan
H
Tian
Yaolan
Y
Li
Wencai
W
Ye
D000255:Adenosine Triphosphate / Q000378:metabolism; D000664:Amphibian Venoms / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002018:Bufanolides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D000664:Amphibian Venoms; D020533:Angiogenesis Inhibitors; D002018:Bufanolides; D042461:Vascular Endothelial Growth Factor A; C055393:arenobufagin; D000255:Adenosine Triphosphate; D040301:Vascular Endothelial Growth Factor Receptor-2