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

绿茶已证明是活体内和体外研究的活性化学预防剂。但是，抑制作用效果的完整机制尚未完全理解。在我们的大多数研究中，绿茶提取物（GTE）及其食道多酚Epigallocatechin（EGC）在Ehrlich腹水肿瘤细胞中显示了肿瘤生长抑制作用，并且已经阐明了几种机制。其中值得注意的是鸟氨酸脱羧酶活性的降低以及细胞谷胱甘肽（GSH）和蛋白质SH水平，细胞硫醇依赖性诱导有丝分裂原活化蛋白激酶的诱导，包括JNK-SAPK，p38和ERK1/2以及MITOCHRIAL ELLICTITY在MITOCHRIAL INCELITY中涉及细胞chrome C释放和分子式激活的变化。我们还观察到，与卵孵育的细胞导致了亚GI和GI细胞周期区域下信号的离散亚群的积累，并且S细胞周期区域的降低。 Futermore，Egg Dec…以剂量依赖性和时间依赖性的方式报道了次磷酸化的视网膜细胞瘤蛋白（RB）水平。用N-ACE泰半半胱氨酸消除了Rb光磷酸化降低的影响，这表明活性氧谱（ROS）涉及绿茶提取物诱导的凋亡。已经观察到ROS参与高度组织的细胞功能，例如信号转导和凋亡的途径。我们观察到，与未处理的细胞相比，与卵孵育后30-60毫米的细胞内过氧化物中暴露于卵子的Ehrlich腹水细胞增加。通过添加过氧化氢酶或NAC，可以提高细胞活力的降低。 GTE导致硫氧还蛋白与Ask1的解离。通过添加NAC或过氧化氢酶消除解离。在肿瘤细胞而不是正常细胞中，清除活性氧，SOD，谷胱甘肽过氧化物酶和过氧化氢酶的酶的活性非常低。因此，通过添加绿茶提取物引起的ROS参与了高度有组织的细胞功能，例如信号转移和凋亡途径。Furthermore通过通过免疫史上的绿茶提取物在人类脐静脉内皮细胞中通过免疫史上的绿色茶提取物在人类脐静脉内部细胞中降低FLT-1和KDR/FLK-1的表达。这些结果表明，通过降低VEGF受体的表达，绿茶提取物可能对肿瘤血管生成和转移具有预防作用。较少的