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Why does the tea extract occur a cell death for tumor cells but not Normal cells?

为什么茶提取物可以使肿瘤细胞死亡，而不能使正常细胞死亡？

基本信息

批准号：
13660133
负责人：
YUASA Isao
金额：
$ 2.24万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13660133/
关键词：
Green tea extract Apoptosis intracellular active oxygen tumor cells cell proliferation tumor angiogenesis signal transduction antioxidative enzymes 抗酸化酵素系血管内皮増殖因子 MAPキナーゼ ASK-1 チオレドキシン茶ポリフェノールグルタチオン細胞周期カスパーゼ Rbタンパク

项目摘要

Green tea has shown to be active chemopreventive agents against cancer both in vivo and in vitro studies. However, the complete mechanisms underlying the inhibitory effects are not fully understood. In most of our studies, the green tea extract (GTE) and its galloyl polyphenols, epigallocatechin (EGC), have shown tumor growth inhibitory effects in Ehrlich ascites tumor cells and several mechanisms have been elucidated. Notable among these include decrease in ornithine decarboxylase activity and in cellular glutathione (GSH) and protein SH levels, cellular thiol-dependent induction of mitogen activated protein kinases including JNK-SAPK, p38 and ERK1/2 and changes in mitochondrial integrity involving cytochrome c release, and subsequent activation of caspase-3-like protease. We also observed that cells incubated with EGG resulted in an accumulation of a discrete sub-population of signals under the sub-Gi and Gi cell cycle regions and a decrease in S cell cycle region. Futermore, EGG dec … More reased hypophosphorylated retinoblastoma protein (Rb) levels in a dose-dependent and time-dependent manner. The effect of Rb phosphorylation decreased by EGG was abolished with N-ace tylcysteine, suggesting that reactive oxygen speaces (ROS) involves in the green tea extract-induced apoptosis. ROS has been observed to take part in highly organized cellular functions like pathways of signal transduction and apoptosis. We observed that Ehrlich ascites tumor cells exposed to EGG increased in intracellular peroxide 30-60 mm after incubation with EGG as compared with non-treated cells. The decrease in cell viability with EGG was improved with the addition of catalase or NAC. GTE caused the dissociation of thioredoxin from ASK1. The dissociation was abolished with the addition of NAC or catalase. In tumor cells but not normal cells, the activities of enzymes scavenging active oxygen, SOD, glutathione peroxidase and catalase, are very low. Therefore, ROS, which are induced with addition of green tea extract, took part in highly organized cellular functions like pathways of signal transduction and apoptosis.Furthermore we found that the decrease of the expression of Flt-1 and KDR/Flk-1 in Human umbilical vein endothelial cells by green tea extract was detected with immunohistoehemical and Western blotting methods. These results suggest that green tea extract may have preventive effects on tumor angiogenesis and metastatis through reduction of expression of VEGF receptors. Less

绿色茶在体内和体外研究中都显示出对癌症的活性化学预防剂。然而，抑制作用的完整机制尚未完全了解。在我们的大多数研究中，绿色茶提取物（GTE）和它的没食子酰多酚，表没食子儿茶素（EGC），显示了对埃利希腹水癌细胞的肿瘤生长抑制作用，并且已经阐明了几种机制。其中值得注意的包括鸟氨酸脱羧酶活性和细胞谷胱甘肽（GSH）和蛋白质SH水平的降低，细胞巯基依赖性诱导促分裂原活化蛋白激酶（包括JNK-SAPK、p38和ERK 1/2），以及涉及细胞色素c释放的线粒体完整性变化，以及随后的半胱天冬酶-3样蛋白酶活化。我们还观察到，与EGG孵育的细胞导致在亚Gi和Gi细胞周期区域下的离散信号亚群的积累和S细胞周期区域的减少。Futermore，EGG dec ...更多信息以剂量依赖和时间依赖的方式降低低磷酸化视网膜母细胞瘤蛋白（Rb）水平。N-乙酰半胱氨酸可阻断EGG对Rb磷酸化的抑制作用，提示活性氧参与了绿色茶提取物诱导的细胞凋亡。已经观察到ROS参与高度组织化的细胞功能，如信号转导和凋亡途径。我们观察到，与未处理的细胞相比，暴露于EGG的埃利希腹水瘤细胞在与EGG孵育后30-60 mm内的细胞内过氧化物增加。加入过氧化氢酶或NAC可改善EGG引起的细胞活力下降。GTE导致硫氧还蛋白从ASK 1解离。加入NAC或过氧化氢酶可消除解离。肿瘤细胞中清除活性氧的酶SOD、谷胱甘肽过氧化物酶和过氧化氢酶的活性很低，而正常细胞则不然。因此，绿色茶提取物诱导的活性氧参与了细胞信号转导和凋亡等高度组织化的细胞功能。此外，我们还通过免疫组化和Western blotting方法检测到绿色茶提取物降低了人脐静脉内皮细胞Flt-1和KDR/Flk-1的表达。这些结果表明，绿色茶提取物可能通过减少VEGF受体的表达而对肿瘤血管生成和转移具有预防作用。少