Matrix metalloproteinase inhibition by green tea catechins

We have investigated the effects of different biologically active component s from natural products, including green tea polyphenols (GTP), resveratrol , genistein and organosulfur compounds from garlic, on matrix metalloprotei nase (MMP)-2, MMP-9 and MRIP-12 activities. GTP caused the strongest inhibi tion 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 wi th both various rat tissues and human brain tumors (glioblastoma and pituit ary tumors). The activities of MMPs were also measured in the presence of v arious catechins isolated from green tea including (-)-epigallocatechin gal late (EGCG), (-)-epicatechin gallate(ECG), (-)-epigallocatechin (EGC), (-)e picatechin (EC) and (+)-catechin (C). The most potent inhibitors of these a ctivities, as measured by fluorescence and by gelatin or casein zymography, were EGCG and EGG. GTP and the different catechins had no effect on pancre atic elastase, suggesting that the effects of these molecules on MMP activi ties are specific. Furthermore, in vitro activation of proMMP-2 secreted fr om the glioblastomas cell line U-87 by the lectin concanavalin A was comple tely inhibited by GTP and specifically by EGCG. These results indicate that catechins from green tea inhibit MMP activities and proMMP-2 activation. ( C) 2000 Elsevier Science B.V. All rights reserved.