(-)-Epigallocatechin gallate inhibits membrane-type 1 matrix metalloproteinase, MT1-MMP, and tumor angiogenesis.
Membrane-type 1 matrix metalloproteinase (MT1-MMP), which hydrolyzes type I collagen and activates MMP-2, are deeply involved in angiogenesis as well as in tumor cell invasion and metastasis. We previously screened a number of natural and synthetic compounds to obtain a specific inhibitor of MT1-MMP and observed that (-)-epigallocatechin gallate (EGCG) has a potent and distinct inhibitory activity against MT1-MMP. In the present study, we investigated the effect of EGCG on tumor angiogenesis. EGCG significantly inhibited the invasion of human umbilical vein endothelial cells (HUVECs) at the concentration of 10 microM. This effect was not due to the toxicity of EGCG since this concentration of EGCG did not affect the HUVEC growth. Furthermore, morphological change of HUVEC at this concentration of EGCG was not observed under confocal laser scanning microscopy. EGCG suppressed tube formation by HUVECs in vitro and angiogenesis in vivo by using dorsal air sac model. Finally, we observed that both colon 26 NL17 carcinoma and Meth A sarcoma growth was suppressed in these tumor-bearing mice by EGCG administration, at least partly though the inhibition of angiogenesis.
Yamakawa
Satoru
S
Department of Medical Biochemistry and COE Program in the 21st Century, School of Pharmaceutical Sciences, University of Shizuoka, Yada, Shizuoka 422-8526, Japan.
Asai
Tomohiro
T
Uchida
Takayuki
T
Matsukawa
Motomi
M
Akizawa
Toshifumi
T
Oku
Naoto
N
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D053511:Matrix Metalloproteinase 14; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008748:Methylcholanthrene; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000517:prevention & control; D012513:Sarcoma, Experimental / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; C507096:Mmp14 protein, mouse; D008748:Methylcholanthrene; D002392:Catechin; C045651:epigallocatechin gallate; D014568:Urokinase-Type Plasminogen Activator; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D053511:Matrix Metalloproteinase 14