Matrix metalloproteinase inhibition by green tea catechins.
We have investigated the effects of different biologically active components from natural products, including green tea polyphenols (GTP), resveratrol, genistein and organosulfur compounds from garlic, on matrix metalloproteinase (MMP)-2, MMP-9 and MMP-12 activities. GTP caused the strongest inhibition of the three enzymes, as measured by fluorescence assays using gelatin or elastin as substrates. The inhibition of MMP-2 and MMP-9 caused by GTP was confirmed by gelatin zymography and was observed for MMPs associated with both various rat tissues and human brain tumors (glioblastoma and pituitary tumors). The activities of MMPs were also measured in the presence of various catechins isolated from green tea including (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate(ECG), (-)-epigallocatechin (EGC), (-)-epicatechin (EC) and (+)-catechin (C). The most potent inhibitors of these activities, as measured by fluorescence and by gelatin or casein zymography, were EGCG and ECG. GTP and the different catechins had no effect on pancreatic elastase, suggesting that the effects of these molecules on MMP activities are specific. Furthermore, in vitro activation of proMMP-2 secreted from the glioblastomas cell line U-87 by the lectin concanavalin A was completely inhibited by GTP and specifically by EGCG. These results indicate that catechins from green tea inhibit MMP activities and proMMP-2 activation.
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Laboratoire de Médecine Moléculaire, Hopital Sainte-Justine - UQAM, C.P. 8888, Succursale centre-ville, Montréal, QC, Canada.
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D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003208:Concanavalin A; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors; D018093:Gelatinases / Q000037:antagonists & inhibitors; D006160:Guanosine Triphosphate / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D015394:Molecular Structure; D013552:Swine; D013662:Tea
D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D061965:Matrix Metalloproteinase Inhibitors; D013662:Tea; D003208:Concanavalin A; D006160:Guanosine Triphosphate; D002392:Catechin; C045651:epigallocatechin gallate; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9