Journal Article

Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation

Sylvie Lamy, Mélanie Blanchette, Jonathan Michaud-Levesque, René Lafleur, Yves Durocher, Albert Moghrabi, Stéphane Barrette, Denis Gingras and Richard Béliveau

in Carcinogenesis

Volume 27, issue 5, pages 989-996
Published in print May 2006 | ISSN: 0143-3334
Published online November 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi279
Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation

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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.

Keywords: bFGF, basic fibroblast growth factor; Cy, cyanidin; Dp, delphinidin; Dp 3-glu, delphinidin 3-O-beta-glucopyranoside; EC, endothelial cell; ERK, extracellular-signal-regulated kinase; HUVEC, human umbilical vein endothelial cell; Mv, malvidin; Pg, pelargonidin; Pn, peonidin; Pt, petunidin; STS, staurosporine; VEGF, vascular endothelial growth factor; VEGFR-2, vascular endothelial growth factor receptor-2

Journal Article.  6105 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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