Premium
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
Author(s) -
Vayalil Praveen K.,
Katiyar Santosh K.
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10352
Subject(s) - du145 , lncap , cancer research , matrix metalloproteinase , p38 mitogen activated protein kinases , phosphorylation , biology , kinase , prostate cancer , protein kinase a , microbiology and biotechnology , medicine , biochemistry , cancer
BACKGROUND Matrix metalloproteinases (MMPs) are involved in tumor progression including the carcinoma of the prostate (CaP). Therefore, the effect of (−)‐epigallocatechin‐3‐gallate (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‐κB 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‐κB. EGCG may play a role in prevention of invasive metastatic processes of both androgen‐dependent and ‐independent prostate carcinoma. © 2003 Wiley‐Liss, Inc.