Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death in men in western world. Overexpression of matrix metalloproteinases (MMPs) has been known to correlate closely with tumor cell invasion and strategies to down-regulate their expression may ultimately be of clinical utility. METHODS. In this study, in vitro invasion assay was performed by incubating various concentrations of 5GG with 2*104 PC-3 cells for 48 h. We investigated the effects of Penta-O-galloyl-beta-D-glucose (5GG), on the cell invasiveness and MMP-9 induction in human androgen-independent prostate cancer PC-3 cells. The anti-invasive and cytotoxic effects of 5GG were evaluated on human prostate cancer PC-3 cell lines by MTT assays and western blot analyses. RESULTS. 5GG inhibited the EGF-induced cell invasiveness and MMP-9 expression in a dose-dependent manner. 5GG treatment was found to reduce the MMP-9 transcriptional activity. To further study the mechanisms for the 5GG-mediated regulation of MMP-9, the effects of 5GG on transcription factor AP-1 and mitogen-activated protein kinase (MAPK) activities were examined. The results showed that 5GG suppressed the EGF-induced NF-kappaB nuclear translocation and also abrogated the EGF-induced activation of c-jun N-terminal kinase (JNK), which an upstream modulators of NF-kappaB. Finally, we showed that 5GG reduced EGFR expression through proteasome pathway. CONCLUSIONS. These results suggest that 5GG may exert at least part of its anti-invasive effect in androgen-independent prostate cancer by controlling MMP expression through the suppression of EGFR/JNK pathway.
