title: Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation.
abstract: Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention.
authors: Laboratoire d'Oncologie Moléculaire, and Centre de Recherche BioMed, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Québec, Canada H3C 3P8, Canada. Electronic address: lamy.sylvie@uqam.ca.
authors: Sylvie
authors: S
authors: Lamy
authors: Laboratoire d'Oncologie Moléculaire, and Centre de Recherche BioMed, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Québec, Canada H3C 3P8, Canada.
authors: Amira
authors: A
authors: Ouanouki
authors: Laboratoire d'Oncologie Moléculaire, and Centre de Recherche BioMed, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Québec, Canada H3C 3P8, Canada.
authors: Richard
authors: R
authors: Béliveau
authors: Laboratoire d'Oncologie Moléculaire, and Centre de Recherche BioMed, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Québec, Canada H3C 3P8, Canada.
authors: Richard R
authors: RR
authors: Desrosiers
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019301:Oleic Acid / Q000494:pharmacology; D000069463:Olive Oil; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D000069463:Olive Oil; D010936:Plant Extracts; D010938:Plant Oils; C005975:3,4-dihydroxyphenylethanol; D019301:Oleic Acid; D011794:Quercetin; C003377:taxifolin; D040301:Vascular Endothelial Growth Factor Receptor-2; D010626:Phenylethyl Alcohol
keywords: Angiogenesis; Endothelial cell; Olive oil; Signaling pathway; VEGF/VEGFR-2