Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells.

摘要: Aberrant epigenetic silencing of the tissue inhibitor matrix metalloproteinase-3 (TIMP-3) gene that negatively regulates metalloproteinases (MMPs) activity has been implicated in pathogenesis and metastasis breast cancer. In present study, we demonstrate green tea polyphenols (GTP) its major constituent, epigallocatechin-3-gallate (EGCG) mediate induction TIMP-3 levels play a key role suppressing invasiveness gelatinolytic MMP-2 MMP-9 cancer cells. Treatment MCF-7 MDA-MB-231 cells with 20 µM EGCG 10 µg/mL GTP for 72 h significantly induces mRNA protein levels. Interestingly, investigations into molecular mechanism revealed repression is mediated by mechanism(s) involving increased enhancer zeste homolog 2 (EZH2) class I histone deacetylases (HDACs), independent promoter DNA hypermethylation. reduced EZH2 HDAC Furthermore, transcriptional activation was found to be associated decreased localization H3K27 trimethylation enrichment at concomitant increase H3K9/18 acetylation. Our findings highlight as event modulated GTPs restoring MMP:TIMP balance delay progression invasion.