Inhibitory effect of green tea polyphenols on membrane-type 1 matrix metalloproteinase, MT1-MMP.
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.
Oku
Naoto
N
Department of Medical Biochemistry and COE Program in the 21st Century, University of Shizuoka, School of Pharmaceutical Sciences.
Matsukawa
Motomi
M
Yamakawa
Satoru
S
Asai
Tomohiro
T
Yahara
Shoji
S
Hashimoto
Fumio
F
Akizawa
Toshifumi
T
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001567:Benzocycloheptenes / Q000737:chemistry / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005780:Gelatin; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins; D013662:Tea / Q000737:chemistry*
D020533:Angiogenesis Inhibitors; D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D001567:Benzocycloheptenes; D005419:Flavonoids; D061965:Matrix Metalloproteinase Inhibitors; D010636:Phenols; D059808:Polyphenols; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D013662:Tea; C000611430:epitheaflagallin 3-O-gallate; C417940:gallocatechin gallate; D002392:Catechin; D005780:Gelatin; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases