Carcinogenesis Advance Access published online on November 23, 2005
Carcinogenesis, doi:10.1093/carcin/bgi279
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1 Laboratoire de Médecine Moléculaire, Hôpital Ste-Justine-Université du Québec à Montréal, Centre de Cancérologie Charles-Bruneau, 3175 Chemin Côte-Ste-Catherine, Montréal, Québec, Canada H3T 1C5
* To whom correspondence should be addressed. Epidemiological studies have shown that a diet rich in fruits and vegetables has a beneficial preventive effect 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 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 signalling 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.
Received May 31, 2005
Revised November 16, 2005
Accepted November 20, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation
Sylvie Lamy 1,
Mélanie Blanchette 1,
Jonathan Michaud-Levesque 1,
René Lafleur 1,
Yves Durocher 2,
Albert Moghrabi 3,
Stéphane Barrette 3,
Denis Gingras 1,
and
Richard Béliveau 1 *
2 Animal Cell Technology Group, Biotechnology Research Institute, National Research Council Canada, 6100 Royalmount Avenue, Montréal, Québec, Canada H4P 2R2
3 Service d'hématologie-oncologie, Centre de Cancérologie Charles-Bruneau, Hôpital Ste-Justine, 3175 Côte-Ste-Catherine, Montréal, Québec, Canada, H3T 1C5
Richard Béliveau, E-mail: molmed{at}recherche-ste-justine.qc.ca
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