Mulberry Polyphenol Extract Inhibits FAK/Src/PI3K Complex and Related Signaling To Regulate the Migration in A7r5 Cells

J Agric Food Chem. 2018 Apr 18;66(15):3860-3869. doi: 10.1021/acs.jafc.8b00958. Epub 2018 Apr 6.

Abstract

Atherosclerosis is characterized by the buildup of plaque inside arteries. Our recent studies demonstrated that polyphenolic natural products can reduce oxidative stress, inflammation, angiogenesis, hyperlipidemia, and hyperglycemia. A previous study also showed that mulberry water extract (MWE) can inhibit atherosclerosis and contains considerable amounts of polyphenols. Therefore, in the present study, we investigated whether mulberry polyphenol extract (MPE) containing high levels of polyphenolic compounds could affect vascular smooth muscle cell (VSMC; A7r5 cell) motility. We found that MPE inhibited expression of FAK, Src, PI3K, Akt, c-Raf, and suppressed FAK/Src/PI3K interaction. Further investigations showed that MPE reduced expression of small GTPases (RhoA, Cdc42, and Rac1) to affect F-actin cytoskeleton rearrangement, down-regulated expression of MMP2 and vascular endothelial growth factor (VEGF) mRNA through NFκB signaling, and thereby inhibited A7r5 cell migration. Taken together, these findings highlight MPE inhibited migration in VSMC through FAK/Src/PI3K signaling pathway.

Keywords: FAK signaling; migration; mulberry; polyphenol; vascular smooth muscle cell.

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Morus / chemistry*
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Polyphenols / isolation & purification
  • Polyphenols / pharmacology*
  • Rats
  • Signal Transduction / drug effects
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • Plant Extracts
  • Polyphenols
  • Phosphatidylinositol 3-Kinases
  • Focal Adhesion Protein-Tyrosine Kinases
  • src-Family Kinases