Mechanisms of inhibition of tumor angiogenesis and vascular tumor growth by epigallocatechin-3-gallate
Mechanisms of inhibition of tumor angiogenesis and vascular tumor growth by epigallocatechin-3-gallate
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DOI：
10.1158/1078-0432.ccr-03-0672
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发表时间：
2004-07-15
影响因子：
11.5
通讯作者：
Albini, A
中科院分区：
文献类型：
--
作者：
Fassina, G;Venè, R;Albini, A
目的：饮用绿色茶与某些肿瘤类型的发生率降低有关。目前的数据表明，这种化学预防作用的主要介质是表没食子儿茶素-3-没食子酸酯（EGCG），干茶叶中发现的最丰富的多酚。在这里，我们研究了这种化合物对两个关键细胞群体的影响，这两个关键细胞群体通常参与肿瘤生长：肿瘤细胞和内皮细胞。实验设计：绿色茶和表没食子儿茶素没食子酸酯（EGCG）的影响在高血管卡波西肉瘤（KS）肿瘤模型中进行了测试，并在一组体内和体外试验中对内皮细胞进行了测试。EGCG在一定剂量范围内抑制KS-IMM细胞生长和内皮细胞生长、趋化性和侵袭;高浓度也诱导肿瘤细胞凋亡。EGCG抑制了金属蛋白酶介导的明胶酶活性产生的内皮细胞上清液和新的毛细血管样结构的形成在体外。当在饮用水中给予小鼠时，绿色茶或纯化的EGCG在Matrigel海绵模型中抑制体内血管生成并抑制KS肿瘤生长。肿瘤的组织学分析是一致的抗血管生成活性的表没食子儿茶素没食子酸酯和绿色tea.Conclusions：这些数据表明，绿色茶没食子酸酯或其衍生物可能会发现使用在预防和治疗血管肿瘤的化学预防或辅助设置。
Purpose: Green tea consumption has been linked to a reduced occurrence of some tumor types. Current data indicate that the principal mediator of this chemopreventive effect is epigallocatechin-3-gallate (EGCG), the most abundant polyphenol found in dried tea leaves. Here, we examined the effects of this compound on the two key cell populations typically involved in tumor growth: tumor cells and endothelial cells.Experimental Design: The effects of green tea and EGCG were tested in a highly vascular Kaposi's sarcoma (KS) tumor model and on endothelial cells in a panel of in vivo and in vitro assays.Results: EGCG inhibited KS-IMM cell growth and endothelial cell growth, chemotaxis, and invasion over a range of doses; high concentrations also induced tumor cell apoptosis. EGCG inhibited the metalloprotease-mediated gelatinolytic activity produced by endothelial cell supernatants and the formation of new capillary-like structures in vitro. Green tea or purified EGCG when administered to mice in the drinking water inhibited angiogenesis in vivo in the Matrigel sponge model and restrained KS tumor growth. Histological analysis of the tumors were consistent with an anti-angiogenic activity of EGCG and green tea.Conclusions: These data suggest that the green tea gallate or its derivatives may find use in the prevention and treatment of vascular tumors in a chemoprevention or adjuvant setting.