title: Resveratrol inhibits migration and Rac1 activation in EGF- but not PDGF-activated vascular smooth muscle cells.
abstract: METHODS
  Migration of vascular smooth muscle cells (VSMC) reflects one of the initial steps in atherosclerosis. Resveratrol (RV) is suggested to mediate putative vasoprotective properties of red wine leading to the hypothesis that RV interferes with growth factor-induced migration of VSMC.
  
  
  RESULTS
  We show here that RV (50 μM) strongly reduces epidermal growth factor (EGF)- but not platelet-derived growth factor (PDGF)-induced VSMC migration using the wound-healing technique. Accordingly, RV inhibited Rac1 activation and lamellipodia formation in response to EGF but not PDGF as shown by pull-down assays and fluorescence microscopy after actin staining with phalloidin-FITC, respectively. Since Src-family kinases and the phosphatidylinositol-3 kinase (PI3K) are reported to be crucial upstream mediators of Rac1 activation we examined the PI3K inhibitor wortmannin and the src kinase inhibitor SU6656 side-by-side with RV for their anti-migratory potential. Whereas src inhibition abrogated both EGF- and PDGF-triggered migration, wortmannin, like RV, was more effective in EGF- than PDGF-activated cells, suggesting that PI3K inhibition, previously shown for RV in growth factor-activated VSMC, contributes to the anti-migratory effect of RV in EGF-stimulated VSMC.
  
  
  CONCLUSIONS
  This study is the first to discover an anti-migratory potential of RV in EGF-activated VSMC that is most likely mediated via Rac1 inhibition.
authors: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors: Mario
authors: M
authors: Kumerz
authors: Elke H
authors: EH
authors: Heiss
authors: Daniel
authors: D
authors: Schachner
authors: Atanas G
authors: AG
authors: Atanasov
authors: Verena M
authors: VM
authors: Dirsch
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D000077191:Wortmannin; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors*
chemical_list: D000730:Androstadienes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor; D013267:Stilbenes; D004815:Epidermal Growth Factor; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D000077185:Resveratrol; D000077191:Wortmannin