Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation.
Epidemiological studies have shown that a diet rich in fruits and vegetables has a beneficial preventive effect on cardiovascular diseases and cancer by mechanisms that have not yet been elucidated. In this work, we investigated the antiangiogenic activities of anthocyanidins, a class of polyphenols present at high levels in fruits. Among the tested anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin), delphinidin was the most potent angiogenic inhibitor. In vitro, low concentrations of delphinidin inhibited vascular endothelial growth factor (VEGF)-induced tyrosine phosphorylation of VEGF receptor (VEGFR)-2, leading to the inhibition of downstream signaling triggered by VEGFR-2. Inhibition of VEGFR-2 by delphinidin inhibited the VEGF-induced activation of ERK-1/2 signaling and the chemotactic motility of human EC as well as their differentiation into capillary-like tubular structures in Matrigel and within fibrin gels. In vivo, delphinidin was able to suppress basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. The identification of delphinidin as a naturally occurring inhibitor of VEGF receptors suggests that this molecule possesses important antiangiogenic properties that may be helpful for the prevention and treatment of cancer.
Lamy
Sylvie
S
Laboratoire de Médecine Moléculaire, Hôpital Ste-Justine-Université du Québec à Montréal, 3175 Côte-Ste-Catherine, Montréal, Québec, Canada, H3T 1C5.
Blanchette
Mélanie
M
Michaud-Levesque
Jonathan
J
Lafleur
René
R
Durocher
Yves
Y
Moghrabi
Albert
A
Barrette
Stéphane
S
Gingras
Denis
D
Béliveau
Richard
R
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000872:Anthocyanins / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008956:Models, Chemical; D009369:Neoplasms / Q000378:metabolism; D010766:Phosphorylation; D011509:Proteoglycans / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000872:Anthocyanins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D040301:Vascular Endothelial Growth Factor Receptor-2; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; C017185:delphinidin