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
- 25 November 2003
- journal article
- research article
- Published by Wiley in The Prostate
- Vol. 59 (1), 33-42
- https://doi.org/10.1002/pros.10352
Abstract
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.Keywords
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