Luteolin inhibited hydrogen peroxide-induced vascular smooth muscle cells proliferation and migration by suppressing the Src and Akt signalling pathways

J Pharm Pharmacol. 2012 Apr;64(4):597-603. doi: 10.1111/j.2042-7158.2011.01438.x. Epub 2011 Dec 29.

Abstract

Objectives: Luteolin is a naturally occurring flavonoid found in many vegetables, fruits and medicinal plants. The migration and proliferation of vascular smooth muscle cells (VSMCs) are the critical pathological processes in various cardiovascular diseases, such as atherosclerosis. In this study, we investigated the effect of luteolin and its latent mechanism on the proliferation and migration of VSMCs stimulated by hydrogen peroxide (H(2) O(2) ).

Methods: VSMC proliferation and cell viability was assayed using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) method or by cell counting, and H(2) O(2) -elicited migration of VSMCs was measured using a transwell migration assay. The phosphorylation levels of Src, 3-phosphoinositide-dependent kinase 1 (PDK1) and Akt (protein kinase B) were analysed by immunoblotting.

Key findings: This study demonstrated that luteolin showed a particularly inhibitory effect on H(2) O(2) -elicited VSMC proliferation and migration. In previous research, we originally explored the function of luteolin in blocking H(2) O(2) -triggered Src and Akt signalling pathways. The activation of Src, PDK1, Akt (308), Akt (473) in the luteolin-treated group was significantly lower than that seen in the H(2) O(2) group.

Conclusions: These findings strongly suggested that luteolin suppresses H(2) O(2) -directed migration and proliferation in VSMCs partially due to down-regulation of the Akt and Src signalling pathways, which are important participants in the processes of migration and proliferation of VSMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Down-Regulation / drug effects
  • Female
  • Hydrogen Peroxide / pharmacology
  • Luteolin / pharmacology*
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • src-Family Kinases / metabolism

Substances

  • Hydrogen Peroxide
  • src-Family Kinases
  • Proto-Oncogene Proteins c-akt
  • Luteolin