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, AKT and mTOR. And further downregulates levels of VEGF, NO, IL-6, IL-8, TNF-α and IFN-γ 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.
Genome Research Laboratory, Delhi Institute of Pharmaceutical Sciences and Research, Pushp Vihar Sec-3, MB Road, New Delhi 110 017, India. saritasaraswati@gmail.com
Sarita
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Saraswati
S S
SS
Agrawal
D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D010946:Plants, Medicinal; D047428:Protein Kinase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013331:Strychnine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D031461:Strychnos nux-vomica / Q000737:chemistry; D013997:Time Factors; D046509:Tissue Culture Techniques; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D016207:Cytokines; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C083806:brucine; D040301:Vascular Endothelial Growth Factor Receptor-2; D013331:Strychnine