Treatment of epigallocatechin-3-gallate inhibits matrix metalloproteinases-2 and -9 via inhibition of activation of mitogen-activated protein kinases, c-jun and NF-κB in human prostate carcinoma DU-145 cells

BACKGROUND. Matrix metalloproteinases (MMPs) are involved in tumor progression including the carcinoma of the prostate (CaP). Therefore, the effect of (-)-epigallocatechin-3gallate (EGCG) was determined on the synthesis and activation of tumor invasion-specific MMP-2 and MMP-9 in human prostate carcinoma DU-145 cells. METHODS. MMP-2 and MMP-9 were determined by zymography and Western blot analysis. Since fibroblast conditioned medium (FCM) partially mimics in vivo tumor-host microenvironment, DU145 cells were co-cultured in FCM. RESULTS. Treatment of EGCG to DU-145 cells resulted in dose-dependent inhibition of FCM-induced pro and active both forms of MMP-2 and MMP-9 concomitant with marked inhibition of phosphorylation of ERK1/2 and p38. In identical conditions, treatment of EGCG or inhibitors of MEK or p38 to DU-145 cells inhibited FCM-induced phosphorylation of ERK1/2 and /or p38 concomitant reduction in MMP-2 and -9. EGCG also inhibited androgen-induced pro-MMP-2 expression in LNCaP cells. Further, treatment of EGCG also resulted in inhibition of activation of c-jun and NF-kappaB in in vitro DU-145 cells. CONCLUSIONS. The inhibition of MMP-2 and MMP-9 in DU145 cells by EGCG is mediated via inhibition of phosphorylation of ERK1/2 and p38 pathways, and inhibition of activation of transcription factors c-jun and NF-kappaB. EGCG may play a role in prevention of invasive metastatic processes of both androgen-dependent and -independent prostate carcinoma. (C) 2003 Wiley-Liss, Inc.