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

在体内和体外研究中，绿茶都被证明是有效的化学防癌剂。然而，抑制作用的完整机制尚不完全清楚。在我们的大多数研究中，绿茶提取物（GTE）及其没食子儿茶素（EGC）在埃利希腹水肿瘤细胞中显示出抑制肿瘤生长的作用，并阐明了几种机制。其中值得注意的包括鸟氨酸脱羧酶活性、细胞谷胱甘肽（GSH）和蛋白SH水平的降低，细胞中有丝分裂原激活蛋白激酶（包括JNK-SAPK、p38和ERK1/2）的细胞硫醇依赖性诱导，涉及细胞色素c释放的线粒体完整性的改变，以及随后的caspase-3样蛋白酶的激活。我们还观察到，用EGG孵育的细胞在亚Gi和Gi细胞周期区域积累了离散的信号亚群，在S细胞周期区域减少。此外，蛋清还以剂量依赖性和时间依赖性的方式增加了低磷酸化的视网膜母细胞瘤蛋白（Rb）水平。N-ace型半胱氨酸可以消除鸡蛋对Rb磷酸化的影响，提示活性氧（ROS）参与了绿茶提取物诱导的细胞凋亡。ROS已被观察到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的埃利希腹水肿瘤细胞在与EGG孵卵30-60 mm后细胞内过氧化水平增加。添加过氧化氢酶或NAC后，卵细胞活力下降的现象得到改善。GTE导致硫氧还蛋白与ASK1分离。添加NAC或过氧化氢酶可消除解离。在肿瘤细胞而非正常细胞中，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都很低。因此，添加绿茶提取物诱导的ROS参与了高度组织化的细胞功能，如信号转导和凋亡途径。免疫组化和Western blotting检测了绿茶提取物对人脐静脉内皮细胞Flt-1和KDR/Flk-1表达的影响。上述结果提示，绿茶提取物可能通过降低VEGF受体的表达，对肿瘤血管生成和转移具有预防作用。少

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