Inhibitory effect of green tea polyphenols on membrane-type 1 matrix metalloproteinase, MT1-MMP.

Abstract	Matrix metalloproteinases (MMPs), especially membrane-type 1 matrix metalloproteinase (MT1-MMP), which generates an active form of MMP-2 from proMMP-2, are deeply involved in angiogenesis as well as in tumor cell migration and metastasis. To obtain a specific inhibitor for MT1-MMP, we screened a number of natural and synthetic compounds using recombinant human MMP-2, MMP-7, and soluble MT1-MMP in a fluorogenic peptide cleavage assay. (-)-Epigallocatechin 3-O-gallate (EGCG) followed by (-)-epigallocatechin 3,5-di-O-gallate and epitheaflagallin 3-O-gallate, was found to have potent and distinct inhibitory activity against MT1-MMP. Therefore, we investigated the effect of EGCG on the suppression of MMP-2 activation as determined by gelatin zymography, and observed that the active form of MMP-2 in the conditioned medium of human umbilical vein endothelial cells was decreased in the presence of EGCG. The results suggest the possibility that tea polyphenols suppress tumor growth through the suppression of angiogenesis.
Authors	Naoto Oku, Motomi Matsukawa, Satoru Yamakawa, Tomohiro Asai, Shoji Yahara, Fumio Hashimoto, Toshifumi Akizawa
Journal	Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 26 Issue 9 Pg. 1235-8 (Sep 2003) ISSN: 0918-6158 [Print] Japan
PMID	12951464 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Angiogenesis Inhibitors Anticarcinogenic Agents Antineoplastic Agents, Phytogenic Benzocycloheptenes Flavonoids Matrix Metalloproteinase Inhibitors Phenols Polyphenols Protease Inhibitors Recombinant Proteins Tea epitheaflagallin 3-O-gallate gallocatechin gallate Catechin Gelatin Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases
Topics	Angiogenesis Inhibitors (pharmacology) Anticarcinogenic Agents (pharmacology) Antineoplastic Agents, Phytogenic (pharmacology) Benzocycloheptenes (chemistry, pharmacology) Catechin (analogs & derivatives, pharmacology) Enzyme Activation (drug effects) Flavonoids (chemistry, pharmacology) Gelatin Humans Matrix Metalloproteinase Inhibitors Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases (antagonists & inhibitors) Phenols (chemistry, pharmacology) Polyphenols (chemistry, pharmacology) Protease Inhibitors (pharmacology) Recombinant Proteins Tea (chemistry)

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