The dietary flavones apigenin and luteolin impair smooth muscle cell migration and VEGF expression through inhibition of PDGFR-beta phosphorylation.
Platelet-derived growth factor (PDGF)-dependent recruitment of mural cells such as pericytes and smooth muscle cells plays a central role in the maturation and stabilization of newly formed vasculature during angiogenesis. In this work, we show that the dietary flavones apigenin and luteolin may interfere with this event through their inhibitory effect on PDGF-dependent phosphorylation of PDGF receptor beta (PDGFR-beta) in smooth muscle cells. Inhibition of PDGFR-beta activity by apigenin and luteolin occurred at low concentrations of the molecules and resulted in the inhibition of extracellular signal-regulated kinase and Akt phosphorylation triggered by PDGF, as well as in a marked reduction of the migratory and invasive properties of these cells. Apigenin and luteolin also strongly inhibit the PDGF-dependent increase in vascular endothelial growth factor (VEGF) mRNA levels and the secretion of VEGF by smooth muscle cells as well as vessel formation in the mouse Matrigel plug assay, suggesting that the inhibitory effects of both molecules on smooth muscle cell function result in impaired angiogenesis. Overall, these results identify apigenin and luteolin as dietary-derived inhibitors of PDGFR-beta activity and suggest that this inhibitory effect may contribute to the chemopreventive properties of these molecules.
Lamy
Sylvie
S
Laboratoire de Médecine Moléculaire, Hôpital Ste-Justine-Université du Québec à Montréal, Québec, Canada.
Bédard
Valérie
V
Labbé
David
D
Sartelet
Hervé
H
Barthomeuf
Chantal
C
Gingras
Denis
D
Béliveau
Richard
R
D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D004032:Diet; D004353:Drug Evaluation, Preclinical; D005260:Female; D047309:Flavones / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D047309:Flavones; D042461:Vascular Endothelial Growth Factor A; D047310:Apigenin; D020797:Receptor, Platelet-Derived Growth Factor beta; D047311:Luteolin