Abstract 1460: Piceatannol suppresses the migration and invasion of DU145 human prostate cancer cells

Abstract

Abstract Piceatannol (trans-3,4,3′,5′-tetrahydroxystilbene) is a polyphenol found in grapes, red wine, Rheum undulatum and seeds of Euphorbia lagascae. The purpose of the present study was to investigate the effects of piceatannol on the migration and invasion characteristics of DU145 prostate cancer cells. DU145 cells were cultured in the presence of 0 − 10 μmol/L piceatannol with or without 10 μg/L epidermal growth factor (EGF). Piceatannol inhibited the basal and EGF-induced cell migration and invasion of DU145 cells. Gelatin zymography and Western blot analysis, Fibrin zymography and real time RT-PCR analysis were conducted using conditioned media and cell extracts. Piceatannol reduced the secretion and mRNA levels of matrix metalloproteinase (MMP)-9, urokinase-type plasminogen activator (uPA), and vascular endothelial growth factor (VEGF). Piceatannol decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels in a concentration-dependent manner. Additionally, piceatannol inhibited the phosphorylation of signal transducer and activator of transcription (STAT)3. Furthermore, piceatannol decreased both basal and EGF-induced secretion of IL-6. IL-6 treatment increased the secretion of uPA and VEGF, the phosphorylation of STAT3, and migration of DU145 cells and these increase were suppressed by piceatannol. An IL-6 nutralizing antibody inhibited the EGF-induced phosphorylation of STAT3 and increase in cell migration and invasion of DU145 cells, which may be mediated via the inhibition of MMP-9 and uPA activities and secretion of VEGF. The inhibition of IL-6/STAT3 activation may be one of the mechanisms by which piceatannol regulates the expression of proteins involved in the rehulation of DU145 cell migration and invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1460.