Inhibitory effects of epigallocatechin-3 gallate, a polyphenol in green tea, on tumor-associated endothelial cells and endothelial progenitor cells

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Abstract

The polyphenol epigallocatechin-3 gallate (EGCG) in green tea suppresses tumor growth by direct action on tumor cells and by inhibition of angiogenesis, but it is not known whether it specifically inhibits tumor angiogenesis. We examined the anti-angiogenic effect of EGCG on tumor-associated endothelial cells (TECs), endothelial progenitor cells (EPCs), and normal endothelial cells (NECs). EGCG suppressed the migration of TECs and EPCs but not NECs. EGCG also inhibited the phosphorylation of Akt in TECs but not in NECs. Furthermore, vascular endothelial growth factor-induced mobilization of EPCs into circulation was inhibited by EGCG. Matrix metalloproteinase-9 (MMP-9) in the bone marrow plasma plays key roles in EPC mobilization into circulation. We observed that expression of MMP-9 mRNA was downregulated by EGCG in mouse bone marrow stromal cells. In vivo model, EGCG suppressed growth of melanoma and reduced microvessel density. Our study showed that EGCG has selective anti-angiogenic effects on TECs and EPC. It is suggested that EGCG could be a promising angiogenesis inhibitor for cancer therapy.

Journal

  • Cancer Science

    Cancer Science 100 (10), 1963-1970, 2009-10

    Wiley-Blackwell

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