Inhibitory effects of epigallocatechin-3 gallate, a polyphenol in green tea, on tumor-associated endothelial cells and endothelial progenitor cells
Inhibitory effects of epigallocatechin-3 gallate, a polyphenol in green tea, on tumor-associated endothelial cells and endothelial progenitor cells
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DOI：
10.1111/j.1349-7006.2009.01255.x
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发表时间：
2009-10-01
期刊：
影响因子：
5.7
通讯作者：
Shindoh, Masanobu
中科院分区：
文献类型：
--
作者：
Ohga, Noritaka;Hida, Kyoko;Shindoh, Masanobu
绿茶中的多酚表没食子儿茶素-3没食子酸酯（EGCG）通过直接作用于肿瘤细胞和抑制血管生成来抑制肿瘤生长，但是否特异性抑制肿瘤血管生成尚不清楚。我们检测了EGCG对肿瘤相关内皮细胞（TEC）、内皮祖细胞（EPC）和正常内皮细胞（NEC）的抗血管生成作用。EGCG抑制TEC和EPC的迁移，但不抑制NEC的迁移。EGCG在TEC中抑制Akt的磷酸化，而在NEC中不抑制。此外，血管内皮生长因子诱导的EPC进入循环被EGCG抑制。骨髓血浆中的MMP-9在EPC动员进入循环中起关键作用。我们观察到EGCG可下调小鼠骨髓基质细胞中MMP-9 mRNA的表达。在体内模型中，EGCG抑制黑色素瘤的生长并降低微血管密度。我们的研究表明，EGCG对TEC和EPC具有选择性的抗血管生成作用。提示EGCG可能是一种很有前途的肿瘤血管生成抑制剂。（癌症科学2009；100:1963-1970）。
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 (TEC), endothelial progenitor cells (EPC), and normal endothelial cells (NEC). EGCG suppressed the migration of TEC and EPC but not NEC. EGCG also inhibited the phosphorylation of Akt in TEC but not in NEC. Furthermore, vascular endothelial growth factor-induced mobilization of EPC into circulation was inhibited by EGCG. 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 an in vivo model, EGCG suppressed growth of melanoma and reduced microvessel density. Our study showed that EGCG has selective anti-angiogenic effects on TEC and EPC. It is suggested that EGCG could be a promising angiogenesis inhibitor for cancer therapy. (Cancer Sci 2009; 100: 1963-1970).