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Mechanism of induction of apoptosis by green tea catechins and tea high-molecular-weight components

绿茶儿茶素及茶叶高分子成分诱导细胞凋亡的机制

基本信息

批准号：
12660119
负责人：
ISEMURA Mamoru
金额：
$ 2.24万
依托单位：
University of Shizuoka
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2003
项目状态：
已结题

项目摘要

It is known that many anti-tumor drugs have apoptosis-inducing activity and apoptosis-inducing compounds may be expected to have potential anti-tumor activity. We have found that green tea catechins and tea high-molecular-weight components have apoptosis-inducing activity. When apoptosis-inducing activity of lipid derivatives of gallic acid was examined in U937 cells, we found the importance of a gallate moiety and hydrophobic nature. We also found apoptosis-inducing activity of an ethanol soluble fraction in driselase digests of green tea residues. In the next experiment, examination of effects of tea components on expression of apoptosis-related genes suggested that the apoptosis-inducing mechanism of a black tea high-molecular-weight component was different from that of EGCG. As for the mechanism of apoptosis induction by EGCG, it was shown that EGCG bound Fas to activate caspase 8, leading to apoptosis. In the in vivo experiments, it was shown that a combination of slindac and EGCG effectively reduced the member of aberrant cript foci in an azoxmethane-induced rat colon cancer model by stimulating apoptosis. Finally, EGCG was found to affect signal transduction through a MAP kinase pathway and to repress expression of matrix metalloproteinase. Thus, the present results encourage the view that intake of green tea is beneficial for cancer prevention.

已知许多抗肿瘤药物具有诱导细胞凋亡的活性，而诱导细胞凋亡的化合物可能具有潜在的抗肿瘤活性。我们发现绿茶儿茶素和茶多糖组分具有诱导细胞凋亡的活性。当检测没食子酸脂类化合物在U937细胞中的诱导凋亡活性时，我们发现没食子酸部分和疏水性的重要性。我们还发现绿茶残渣Driselase消化液中的乙醇可溶部分具有诱导细胞凋亡的活性。在接下来的实验中，检测了茶叶成分对凋亡相关基因表达的影响，表明红茶高分子成分的诱导凋亡机制与EGCG不同。关于EGCG诱导细胞凋亡的机制，研究表明，EGCG与Fas结合激活caspase8，导致细胞凋亡。体内实验表明，Slindac和EGCG联用可通过刺激细胞凋亡，有效地减少偶氮甲烷诱导的大鼠结肠癌模型中异常转录部位的成员。最后，发现EGCG通过MAP激酶途径影响信号转导，并抑制基质金属蛋白酶的表达。因此，目前的结果支持了这样一种观点，即摄入绿茶有助于预防癌症。