|Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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
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