Brucine, an indole alkaloid from Strychnos nux-vomica attenuates VEGF-induced angiogenesis via inhibiting VEGFR2 signaling pathway in vitro and in vivo

In this study, we investigated the mechanism of brucine in tumor angiogenesis. We found that brucine inhibits VEGF-induced cell proliferation, chemotactic motility, and the formation of capillary-like structures in HUVECs in a dose-dependent manner. Brucine suppresses VEGF- induced p-VEGFR2 kinase activity and inhibits neovascularization in vivo. Brucine inhibits the downstream protein kinases of VEGFR2, including Src, FAK, ERK, ART and mTOR. And further downregulates levels of VEGF, NO, IL-6, IL-8, TNF-alpha, and IFN-gamma in HUVECs. Taken together, our study suggests that brucine potently suppresses angiogenesis by targeting VEGFR2 activation and may be a viable drug candidate in anti-angiogenesis and anti-cancer therapies. (C) 2013 Elsevier Ireland Ltd. All rights reserved.