Arenobufagin, a bufadienolide compound from toad venom, inhibits VEGF-mediated angiogenesis through suppression of VEGFR-2 signaling pathway

作者：Li, Manmei; Wu, Shuai; Liu, Zhong; Zhang, Wei; Xu, Jing; Wang, Ying; Liu, Junshan; Zhang, Dongmei; Tian, Haiyan; Li, Yaolan; Ye, Wencai^*

来源：Biochemical Pharmacology, 2012, 83(9): 1251-1260.

DOI：10.1016/j.bcp.2012.01.023

• Arenobufagin
• Angiogenesis
• Vascular endothelial growth factor (VEGF)
• Vascular endothelial growth factor receptor 2 (VEGFR-2)

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.

• 出版日期2012-5-1
• 单位暨南大学