title: EGCG blocks tumor promoter-induced MMP-9 expression via suppression of MAPK and AP-1 activation in human gastric AGS cells.
abstract: 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. In this study, we investigated the effects of (-)-epigallocatechin gallate (EGCG), a major green tea catechin, on the cell invasiveness and MMP-9 induction in human gastric cancer AGS cells. EGCG inhibited the phorbol 12-myristate 13-acetate (PMA)-induced cell invasiveness and MMP-9 expression in a dose-dependent manner. EGCG treatment was found to reduce the MMP-9 transcriptional activity. To further study the mechanisms for the EGCG-mediated regulation of MMP-9, the effects of EGCG on transcription factor AP-1 and mitogen-activated protein kinase (MAPK) activities were examined. The results showed that EGCG suppressed the PMA-induced AP-1 activation. EGCG also abrogated the PMA-induced activation of extracellular-regulated protein kinase (Erk) and c-jun N-terminal kinase (JNK), which are upstream modulators of AP-1. These results suggest that EGCG may exert at least part of its anti-invasive effect in gastric cancer by controlling MMP expression through the suppression of MAPK and AP-1 activation.
authors.affiliation: Chonnam University Research Institute of Medical Sciences, Chonnam National University Medical School, Kwangju, Korea.
authors.forename: Hong S
authors.initials: HS
authors.lastname: Kim
authors.forename: Mi H
authors.initials: MH
authors.lastname: Kim
authors.forename: Min
authors.initials: M
authors.lastname: Jeong
authors.forename: Young S
authors.initials: YS
authors.lastname: Hwang
authors.forename: Sun H
authors.initials: SH
authors.lastname: Lim
authors.forename: Boo A
authors.initials: BA
authors.lastname: Shin
authors.forename: Bong W
authors.initials: BW
authors.lastname: Ahn
authors.forename: Young D
authors.initials: YD
authors.lastname: Jung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D061965:Matrix Metalloproteinase Inhibitors; D018808:Transcription Factor AP-1; D002392:Catechin; C045651:epigallocatechin gallate; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate