Phosphoinositide 3-kinase is a novel target of piceatannol for inhibiting PDGF-BB-induced proliferation and migration in human aortic smooth muscle cells

Keun Hwa Choi, Jong Eun Kim, Nu Ry Song, Joe Eun Son, Mun Kyung Hwang, Sanguine Byun, Jong Hun Kim, Ki Won Lee, Hyong Joo Lee

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

AimsAbnormal migration and proliferation of human aortic smooth muscle cells (HASMCs) to the intima causes intimal thickening of the aorta, which is strongly related to the development of atherosclerosis. Previous studies have suggested that red wine polyphenols, particularly resveratrol, have great protective effects against cardiovascular diseases. Here, we compared the anti-atherosclerotic effect of piceatannol, a metabolite of resveratrol, and its underlying mechanisms.Methods and resultsWe demonstrated that piceatannol inhibited platelet-derived growth factor (PDGF)-BB-induced cell migration using a modified Boyden chamber assay and wound healing assay. Western blot analysis showed that PDGF-BB-induced phosphorylation of Akt, p70S6K, and p38 was inhibited by piceatannol, but not resveratrol. In vitro and ex vivo phosphoinositide 3-kinase (PI3K) assays demonstrated that piceatannol suppressed PI3K activity more effectively than resveratrol. PDGF-BB-induced migration and proliferation of HASMCs were inhibited by treatment with a commercial PI3K inhibitor, LY294002. Both in vitro and ex vivo pull-down assays revealed that piceatannol directly binds with sepharose 4B-PI3K beads in an ATP-competitive manner.ConclusionThe results of the present study demonstrate that piceatannol directly binds with PI3K in an ATP-competitive manner and suppresses PI3K activity with anti-atherosclerotic effects.

Original languageEnglish
Pages (from-to)836-844
Number of pages9
JournalCardiovascular Research
Volume85
Issue number4
DOIs
Publication statusPublished - 2010 Mar 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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