Inhibition of proliferation and migration by piceatannol in vascular smooth muscle cells

Piceatannol (3,5,3’,4’-tetrahydroxy- trans-stilbene), a resveratrol analogue, is a polyphenol present in the skins of grapes and in wine and other foods. The present study aimed to investigate for the first time the cardioprotective effects of piceatannol on vascular smooth muscle cells (VSMC). The treatment of cells with piceatannol inhibited cell proliferation by reducing extracellular signal-regulated kinase (ERK) 1/2 and JNK activity in cultured VSMC in the presence of tumor necrosis factor-α (TNF-α). These inhibitory effects were also associated with G1 cell cycle arrest, and resulted in a decrease in cyclin-dependent kinases (CDKs) and cyclins. Piceatannol treatment strongly induced the expression of p21WAF1 via independence of p27KIP and p53 expression. The effect of piceatannol was not restricted to cell proliferation, as TNF-α-induced invasion and migration was also suppressed in VSMC. Moreover, piceatannol treatment strongly decreased matrix metalloproteinase-9 (MMP-9) expression and promoter activity in a dose-dependent manner in response to TNF-α. It was further demonstrated that piceatannol abrogated the transcriptional activity of nuclear factor kappa B (NF-κB), an important nuclear transcription factor involved in MMP-9 expression. Overall, these results demonstrate that piceatannol inhibits proliferation and migration of VSMC treated with TNF-α. Therefore, piceatannol may be an effective therapeutic approach to treat atherosclerosis.