Lowbush Blueberry Component Pterostilbene Inhibits the Matrix Metalloproteinase and the Urokinase Signaling Systems in Human Prostate Cancer Cells Via Alterations in Cellular Signal Transduction Pathways

Abstract

Wild blueberry extracts were shown to inhibit MMP-2 & MMP-9 activity in DU145 human prostate cancer cells in vitro. This study examined the effects of pterostilbene (PT) on MMP & uPA activities in DU145 cells. PT (30uM)(6h) inhibited MMP-2/-9 activity. PT decreased cellular viability ~10% post 6 h. exposure. PT treatment increased TIMP-1/-2 & decreased EMMPRIN & RECK expression. PT treatment decreased uPA & uPAR and increased PAI-1/-2 protein expression. PT treatment resulted in increased expression of pERK-1, pERK-2 & ERK-1. PT decreased p-p38 & p38 protein levels. No apparent change in either ERK-2, JNK-1 & JNK-2 or p-JNK-2 expression was noted. PT did increase p-JNK-1 protein levels. PT increased expression of p-Akt & P-I-3 kinase p85 with no apparent change in either Akt or P-I-3 kinase p110 protein expression levels. PT also increased JAK1, STAT3 & STAT4 expression & decreased JAK2 & STAT1 expression with no apparent change in either JAK3 or STAT2 expression. PT decreased cytosolic p65 and nuclear p50 & increased cytosolic p50 & increased IkB & c-fos and c-jun expression. PT can inhibit MMP-2/-9 & uPA activities by affecting cellular signalling. (Telus Motorcycle Ride for Dad (PEI Division) Prostate Cancer Research Fund)