Carcinogenesis Advance Access originally published online on November 23, 2005
Carcinogenesis 2006 27(5):989-996; doi:10.1093/carcin/bgi279
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Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation
1 Laboratoire de Médecine Moléculaire, Hôpital Ste-Justine-Université du Québec à Montréal and 2 Service d'hématologie–oncologie, Centre de Cancérologie Charles-Bruneau, Hôpital Ste-Justine, 3175 Côte-Ste-Catherine, Montréal, Québec, Canada, H3T 1C5 and 3 Animal Cell Technology Group, Biotechnology Research Institute, National Research Council Canada, 6100 Royalmount Avenue, Montréal, Québec, Canada H4P 2R2
* To whom correspondence should be addressed at: Laboratoire de Médecine Moléculaire, Centre de Cancérologie Charles-Bruneau, Hôpital Ste-Justine, 3175 Côte Ste-Catherine, Montréal, Québec, Canada H3T 1C5; Email: molmed{at}recherche-ste-justine.qc.ca
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.
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