(−)-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 μM. 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.