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EGCG
Terms modified by EGCG Selected AbstractsAdvanced glycation end products-induced apoptosis attenuated by PPAR, activation and epigallocatechin gallate through NF-,B pathway in human embryonic kidney cells and human mesangial cellsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2010Yao-Jen Liang Abstract Background Diabetic nephropathy has attracted many researchers' attention. Because of the emerging evidence about the effects of advanced glycation end products (AGEs) and receptor of AGE (RAGE) on the progression of diabetic nephropathy, a number of different therapies to inhibit AGE or RAGE are under investigation. The purpose of the present study was to examine whether peroxisome proliferator-activated receptor , (PPAR,) agonist (L-165041) or epigallocatechin gallate (EGCG) alters AGE-induced pro-inflammatory gene expression and apoptosis in human embryonic kidney cells (HEK293) and human mesangial cells (HMCs). Methods The HEK cells and HMC were separated into the following groups: 100 µg/mL AGE alone for 18 h; AGE treated with 1 µM L-165041 or 10 µM EGCG, and untreated cells. Inflammatory cytokines, nuclear factor-,B pathway, RAGE expression, superoxide dismutase and cell apoptosis were determined. Results AGE significantly increased tumour necrosis factor-, (TNF-,), a major pro-inflammatory cytokine. The mRNA and protein expression of RAGE were up-regulated. These effects were significantly attenuated by pre-treatment with L-165041 or EGCG. AGE-induced nuclear factor-,B pathway activation and both cells apoptosis were also inhibited by L-165041 or EGCG. Furthermore, both L-165041 and EGCG increased superoxide dismutase levels in AGE-treated HEK cells and HMC. Conclusions This study demonstrated that PPAR, agonist and EGCG decreased the AGE-induced kidney cell inflammation and apoptosis. This study provides important insights into the molecular mechanisms of EGCG and PPAR, agonist in attenuation of kidney cell inflammation and may serve as a therapeutic modality to treat patients with diabetic nephropathy. Copyright © 2010 John Wiley & Sons, Ltd. [source] Carbonyl reductase 1 as a novel target of (,)-epigallocatechin gallate against hepatocellular carcinoma,HEPATOLOGY, Issue 2 2010Weixue Huang Human carbonyl reductase 1 (CBR1) converts the antitumor drug and anthracycline daunorubicin (DNR) into the alcohol metabolite daunorubicinol (DNROL) with significantly reduced antitumor activity and cardiotoxicity, and this limits the clinical use of DNR. Inhibition of CBR1 can thus increase the efficacy and decrease the toxicity of DNR. Here we report that (,)-epigallocatechin gallate (EGCG) from green tea is a promising inhibitor of CBR1. EGCG directly interacts with CBR1 and acts as a noncompetitive inhibitor with respect to the cofactor reduced nicotinamide adenine dinucleotide phosphate and the substrate isatin. The inhibition is dependent on the pH, and the gallate moiety of EGCG is required for activity. Molecular modeling has revealed that EGCG occupies the active site of CBR1. Furthermore, EGCG specifically enhanced the antitumor activity of DNR against hepatocellular carcinoma SMMC7721 cells expressing high levels of CBR1 and corresponding xenografts. We also demonstrated that EGCG could overcome the resistance to DNR by Hep3B cells stably expressing CBR1 but not by RNA interference of CBR1-HepG2 cells. The level of the metabolite DNROL was negatively correlated with that of EGCG in the cell extracts. Finally, EGCG decreased the cardiotoxicity of DNR in a human carcinoma xenograft model with both SMMC7721 and Hep3B cells in mice. Conclusion: These results strongly suggest that EGCG can inhibit CBR1 activity and enhance the effectiveness and decrease the cardiotoxicity of the anticancer drug DNR. These findings also indicate that a combination of EGCG and DNR might represent a novel approach for hepatocellular carcinoma therapy or chemoprevention. (HEPATOLOGY 2010;) [source] The combination of epigallocatechin gallate and curcumin suppresses ER,-breast cancer cell growth in vitro and in vivoINTERNATIONAL JOURNAL OF CANCER, Issue 9 2008Tiffany J. Somers-Edgar Abstract Both epigallocatechin gallate (EGCG) and curcumin have shown efficacy in various in vivo and in vitro models of cancer. This study was designed to determine the efficacy of these naturally derived polyphenolic compounds in vitro and in vivo, when given in combination. Studies in MDA-MB-231 cells demonstrated that EGCG + curcumin was synergistically cytotoxic and that this correlated with G2/M-phase cell cycle arrest. After 12 hr, EGCG (25 ,M) + curcumin (3 ,M) increased the proportion of cells in G2/M-phase to 263 ± 16% of control and this correlated with a 50 ± 4% decrease in cell number compared to control. To determine if this in vitro result would translate in vivo, athymic nude female mice were implanted with MDA-MB-231 cells and treated with curcumin (200 mg/kg/day, po), EGCG (25 mg/kg/day, ip), EGCG + curcumin, or vehicle control (5 ml/kg/day, po) for 10 weeks. Tumor volume in the EGCG + curcumin treated mice decreased 49% compared to vehicle control mice (p < 0.05), which correlated with a 78 ± 6% decrease in levels of VEGFR-1 protein expression in the tumors. Curcumin treatment significantly decreased tumor protein levels of EGFR and Akt, however the expression of these proteins was not further decreased following combination treatment. Therefore, these results demonstrate that the combination of EGCG and curcumin is efficacious in both in vitro and in vivo models of ER,- breast cancer and that regulation of VEGFR-1 may play a key role in this effect. © 2007 Wiley-Liss, Inc. [source] Inhibition of tumour invasion and angiogenesis by epigallocatechin gallate (EGCG), a major component of green teaINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2001Young D. Jung Epidemiological studies have suggested that consumption of green tea may decrease cancer risk. In addition, abundant pre-clinical data from several laboratories have provided convincing evidence that polyphenols present in green tea afford protection against cancer in both in vivo and in vitro studies. Recently, epigallocatechin gallate (EGCG), a putative chemopreventive agent and a major component of green tea, was reported to inhibit tumour invasion and angiogenesis, processes that are essential for tumour growth and metastasis. Understanding the basic principles by which EGCG inhibits tumour invasion and angiogenesis may lead to the development of new therapeutic strategies, in addition to supporting the role of green tea as a cancer chemopreventive agent. [source] (,)Epigallocatechingallate protects the mitochondria against the deleterious effects of lipids, calcium and adenosine triphosphate in isoproterenol induced myocardial infarcted male Wistar ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 8 2008P. T. Devika Abstract The present study was undertaken to evaluate the protective effect of (,)epigallocatechin gallate (EGCG) on mitochondrial lipids, lipid peroxides, Na+/K+ ATPase, calcium and adenosine triphosphate in isoproterenol (ISO) induced myocardial infarction in male Wistar rats. Rats were pretreated with EGCG (30 mg kg,1 body weight) orally using an intragastric tube daily for a period of 21 days. After that, ISO (100 mg kg,1 body weight) was subcutaneously injected to rats at intervals of 24 h for two days. ISO induced rats showed significant increase in the levels of cholesterol, triglycerides and free fatty acids with subsequent decrease in the levels of phospholipids in mitochondrial fraction of the heart. ISO induction also caused significant increase in lipid peroxidation products (thiobarbituric acid reactive substances and lipid hydroperoxides) and significant decrease in the activity of Na+/K+ ATPase in mitochondrial fraction of the heart. A significant increase in the levels of calcium and significant decrease in the levels of adenosine triphosphate were observed in ISO-induced mitochondrial heart. Prior treatment with EGCG (30 mg kg,1) significantly protected these alterations and maintained normal mitochondrial function. Thus, this study confirmed the protective effect of EGCG on mitochondria in experimentally induced cardiotoxicity in Wistar rats. Copyright © 2008 John Wiley & Sons, Ltd. [source] The green tea compound, (,)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2007Kimberly M. Rieger-Christ Abstract Green tea has been reported as potential dietary protection against numerous cancers and has been shown to have activity in bladder tumor inhibition in different animal models. The goal of this study was to examine the effects of (,)-epigallocatechin gallate (EGCG,the major phytochemical in green tea) on growth inhibition and behavior of human bladder carcinoma cells and to identify the altered signaling pathway(s) underlying the response to EGCG exposure. EGCG inhibited the in vitro growth of invasive bladder carcinoma cells with an IC50 range of 70,87 µM. At a concentration of 20 µM, EGCG decreased the migratory potential of bladder carcinoma cells with concomitant activation of p42/44 MAPK and STAT3 and inactivation of Akt. Using biochemical inhibitors of MAPK/ERK, and siRNA to knockdown STAT3 and Akt, inhibition of migration was recorded associated with Akt but not MAPK/ERK or STAT3 signaling in bladder cells. In addition, EGCG downregulated N-cadherin in a dose-dependent manner where reduction in N-cadherin expression paralleled declining migratory potential. Continuous feeding of EGCG to mice prior to and during the establishment of bladder carcinoma xenografts in vivo revealed >50% reduction in mean final tumor volume (P,,,0.05) with no detectable toxicity. EGCG inhibited bladder carcinoma cell growth and suppressed the in vitro migration capacity of cells via downregulation of N-cadherin and inactivation of Akt signaling. Continuous administration of EGCG to mice revealed significant inhibition of tumor growth in vivo indicating a possible preventative role for green tea in bladder cancer. J. Cell. Biochem. 102: 377,388, 2007. © 2007 Wiley-Liss, Inc. [source] Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in cultureJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2001Kathryn T. Kavanagh Abstract Epidemiological evidence suggests tea (Camellia sinensis L.) has chemopreventive effects against various tumors. Green tea contains many polyphenols, including epigallocatechin-3 gallate (EGCG), which possess anti-oxidant qualities. Reduction of chemically induced mammary gland carcinogenesis by green tea in a carcinogen-induced rat model has been suggested previously, but the results reported were not statistically significant. Here we have tested the effects of green tea on mammary tumorigenesis using the 7,12-dimethylbenz(a)anthracene (DMBA) Sprague-Dawley (S-D) rat model. We report that green tea significantly increased mean latency to first tumor, and reduced tumor burden and number of invasive tumors per tumor-bearing animal; although, it did not affect tumor number in the female rats. Furthermore, we show that proliferation and/or viability of cultured Hs578T and MDA-MB-231 estrogen receptor-negative breast cancer cell lines was reduced by EGCG treatment. Similar negative effects on proliferation were observed with the DMBA-transformed D3-1 cell line. Growth inhibition of Hs578T cells correlated with induction of p27Kip1 cyclin-dependent kinase inhibitor (CKI) expression. Hs578T cells expressing elevated levels of p27Kip1 protein due to stable ectopic expression displayed increased G1 arrest. Thus, green tea had significant chemopreventive effects on carcinogen-induced mammary tumorigenesis in female S-D rats. In culture, inhibition of human breast cancer cell proliferation by EGCG was mediated in part via induction of the p27Kip1 CKI. J. Cell. Biochem. 82:387,398, 2001. © 2001 Wiley-Liss, Inc. [source] Epigallocatechin gallate attenuates experimental non-alcoholic steatohepatitis induced by high fat dietJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8pt2 2008Nalan Kuzu Abstract Background and Aim:, In the present study, we examined the preventive role of epigallocatechin gallate (EGCG) in an experimental non-alcoholic steatohepatitis model induced by a high fat diet. Methods:, The study included 21 male Sprague-Dawley rats, which were equally divided into three groups. The first group was fed on a standard rat diet, the second group on a high fat diet (HFD), and the third group on a HFD + EGCG. The study concluded after 6 weeks. Histopathological examination was performed. Plasma and tissue MDA levels, glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, triglyceride, and cholesterol levels were studied. Insulin resistance was calculated by the homeostasis model of insulin resistance method. Results:, Steatosis, inflammation, ballooning degeneration, and necrosis increased significantly in the HFD group, compared to the control group (P < 0.01). Steatosis and inflammation decreased in the HFD + EGCG group, in comparison to the HFD group (P < 0.05, for each). There was a significant decline in ALT (P < 0.01), triglyceride (P < 0.01), insulin (P < 0.05), and glucose (P < 0.05) levels in the HFD + EGCG group, when compared to the HFD group. Plasma and liver MDA levels in the HFD + EGCG group were lower than those of the HFD group; the difference was significant (P < 0.01 for each). Glutathione levels in the HFD + EGCG group was significantly higher those in the HFD group. CYP 2E1 and ,-smooth muscle actin expression decreased in the HFD + EGCG group, in comparison to the HFD group (P < 0.01, P < 0.05, respectively). Conclusion:, EGCG reduces the development of experimental non-alcoholic steatohepatitis induced by a high fat diet. It seems to exercise this effect through its effect on lipid metabolism and antioxidant characteristics. [source] c-DNA Microarray to determine molecular events in neurodegeneration and neuroprotectionJOURNAL OF NEUROCHEMISTRY, Issue 2002M. B. H. Youdim Cell death in CNS involves complex processes, many of which have not been identified biochemically. At the present biochemical techniques cannot adequately establish these. However, the advent of cDNA microarray or microchips, in which the expression of thousands of genes can be measured at once to give a global assessment in disease pathology, its progress or animal models, has simplified this. We have employed this technique to study the mechanism of neurotoxicity of MPTP and 6-hydroxydoapmine induced in neuronally derived cells in culture, in the animal models of Parkinson's disease and neuroprotection initiated by monoamine oxidase B inhibitor, rasagiline; iron chelators, R-apomorphine and EGCG and other neuroprotective drugs. Our studies have clearly indicated that MPTP induced early gene expression, prior to cell death (first 24 h), are prerequirement for 51 late gene expression changes implicated at the time of neuronal death. The latter genes include those involved in iron metabolism, oxidative stress, inflammatory processes, glutaminergic excitotoxicity, nitric oxide, growth factors, transcription factors, cell cycle, intermediatory metabolism and other gene previously not identified. The expressions of many of the latter genes, also identified by in situ hybridization, are prevented when the animals are pretreated with the above neuroprotective drugs. These studies have clearly shown that neurodegeneratrion is a complex cascades of ,domino' effect. Thus a single neuroprotective drug treatment may not be adequate to prevent it, but, that a cocktail of drugs might. [source] Inhibitory effects of green tea polyphenol (,)-epigallocatechin gallate on the expression of matrix metalloproteinase-9 and on the formation of osteoclastsJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2004Jeong-Ho Yun Background:, Alveolar bone resorption is a characteristic feature of periodontal diseases and involves the removal of both the mineral and organic constituents of the bone matrix, which is caused by either multinucleated osteoclast cells or matrix metalloproteinases (MMPs). The gram-negative bacterium, Porphyromonas gingivalis has been reported to stimulate the activity and expression of several groups of MMPs, whereas (,)-epigallocatechin gallate (EGCG), the main constituent of green tea polyphenols, has been reported to have inhibitory effects on the activity and expression of MMPs. Objectives:, In the present study, we investigated the effects of the green tea polyphenol, EGCG, on the gene expression of osteoblast-derived MMP-2, -9 and -13, stimulated by P. gingivalis, and on the formation of osteoclasts. Methods:, The effect of EGCG on the gene expression of MMPs was examined by treating mouse calvarial primary osteoblastic cells with EGCG (20 µm) in the presence of sonicated P. gingivalis extracts. The transcription levels of MMP-2, -9 and -13 were assessed by reverse transcription-polymerase chain reaction (RT-PCR). The effect of EGCG on osteoclast formation was confirmed by tartrate-resistant acid phosphatase (TRAP) staining in a co-culture system of mouse bone marrow cells and calvarial primary osteoblastic cells. Results:, Treatment with the sonicated P. gingivalis extracts stimulated the expression of MMP-9 mRNA and this effect was significantly reduced by EGCG, whereas the transcription levels of MMP-2 and MMP-13 were not affected by either the sonicated P. gingivalis extracts or EGCG. In addition, EGCG significantly inhibited osteoclast formation in the co-culture system at a concentration of 20 µm. Conclusions:, These findings suggest that EGCG may prevent the alveolar bone resorption that occurs in periodontal diseases by inhibiting the expression of MMP-9 in osteoblasts and the formation of osteoclasts. [source] Reversal of cancer multidrug resistance by green tea polyphenolsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2004Yuying Mei The aim of this study was to examine the effect and mechanism of green tea polyphenols (TP) on reversal of multidrug resistance (MDR) in a carcinoma cell line. Using the MTT assay, TP was examined for its modulating effects on the drug-resistant KB-A-1 cells and drug-sensitive KB-3,1 cells. When 10 ,g mL,1 (-)-epigallocatechin gallate (EGCG) or 40 ,g mL,1 TP were present simultaneously with doxorubicin (DOX), the IC50 of DOX on KB-A-1 cells decreased from 10.3 ± 0.9 ,g mL,1 to 4.2 ± 0.2 and 2.0 ± 0.1 ,g mL,1, respectively. TP and EGCG enhanced the DOX cytotoxicity on KB-A-1 cells by 5.2-and 2.5-times, respectively, but did not show a modulating effect on KB-3,1 cells. This indicated that both TP and EGCG had reversal effects on the MDR phenotype in-vitro. A KB-A-1 cell xenograft model was established, and the effect of TP on reversing MDR in-vivo was determined. Mechanistic experiments were conducted to examine the uptake, efflux and accumulation of DOX. Cloning and expression of the nucleotide binding domain of the human MDR1 gene in Escherichia coli was established, and by using colorimetry to examine the activity of ATPase to hydrolyse ATP, the ATPase activity of target nucleotide binding domain protein was determined. TP exerted its reversal effects through the inhibition of ATPase activity, influencing the function of P-glycoprotein, and causing a decreased extrusion of anticancer drug and an increased accumulation of anticancer drug in drug resistant cells. Using reverse transcription-polymerase chain reaction, the inhibitory effect of TP on MDR1 gene expression was investigated. Down-regulation of MDR1 gene expression was the main effect, which resulted in the reversal effect of TP on the MDR phenotype. TP is a potent MDR modulator with potential in the treatment of P-glycoprotein mediated MDR cancers. [source] The development of a suitable manufacturing process for ,Benifuuki' green tea beverage with anti-allergic effectsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 10 2005Hiroshi Nagai Abstract Epigallocatechin-3- O -(3- O -methyl) gallate (EGCG3,Me) has been reported to inhibit type I allergy better than epigallocatechin gallate (EGCG), a major catechin in tea leaves (Camellia sinensis L). We examined the effects of extraction and sterilization on the catechin content and histamine release from mast cells, as a representative reaction of early phase allergy, in the manufacture of ,Benifuuki' green tea beverage. Among various varieties of tea, the cultivar ,Benifuuki' contains approximately 2% of EGCG3,Me. Ester-type catechins and their epimers increased with the increased extraction temperature of the tea. A tea infusion, extracted at 90 °C, strongly inhibited histamine release from mast cells. Furthermore, sterilization affected the catechin content in the manufactured green tea beverage. Sterilization at high temperature promoted the isomerization of catechins and the sterilized green tea beverage had a strong inhibitory effect. When EGCG3,Me, EGCG, epicatechin-3- O -gallate (ECG) and their epimers, GCG3,Me (gallocatechin-3- O -(3- O -methyl) gallate), GCG (gallocatechin-3- O -gallate) and CG (catechin-3- O -gallate) were compared, the anti-allergic effect of GCG3,Me was strongest, and the order of activity was GCG3,Me > EGCG3,Me > GCG > EGCG. We consequently suggest that it was necessary to extract components from tea at the highest temperature possible, and to pasteurize under retort conditions (118.1 °C, 20 min), to manufacture functional green tea beverage with an anti-allergic action. Copyright © 2005 Society of Chemical Industry [source] Soil moisture stress-induced alterations in bioconstituents determining tea qualityJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 12 2003PR Jeyaramraja Abstract The impact of water stress on the biochemical constituents that determine black tea quality was investigated. Phenylalanine ammonia lyase (PAL) activity was highest in the drought tolerant ,Assam' cultivar UPASI-2, followed by UPASI-8 and UPASI-9, under non-stress conditions. Under soil moisture stress a reduction in PAL activity was found in all three clones investigated. A strong positive correlation was observed between an increase in soil moisture deficit and a decrease in PAL activity. Lower PAL activity correlated well with lower synthesis of flavanols such as epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), which are important precursors of theaflavin-3,3,-digallate that determines final tea quality. Altered synthesis of EGCG and ECG could be due to their molecular rearrangement at elevated leaf temperature during drought. Synthesis of quality constituents such as gallic acid and caffeine declined significantly owing to both drought and waterlogging stress. The reduction in gallic acid due to water stress could lead to lower synthesis of theaflavin fractions such as epitheaflavic acid, epitheaflavic acid-3,-gallate and theaflavic acid and, thereby, quality deterioration. Similarly to drought, flooding stress was also found to alter the biochemical constituents necessary for tea quality. Copyright © 2003 Society of Chemical Industry [source] Short-term administration of (-)-epigallocatechin gallate reduces hepatic steatosis and protects against warm hepatic ischemia/reperfusion injury in steatotic miceLIVER TRANSPLANTATION, Issue 3 2005Ryan N. Fiorini Hepatic steatosis increases the extent of cellular injury incurred during ischemia/reperfusion (I/R) injury. (-)-Epigallocatechin gallate (EGCG), the major flavonoid component of green tea (camellia sinensis) is a potent antioxidant that inhibits fatty acid synthase (FAS) in vitro. We investigated the effects of EGCG on hepatic steatosis and markers of cellular damage at baseline and after I/R injury in ob/ob mice. Animals were pretreated with 85 mg/kg EGCG via intraperitoneal (ip) injection for 2 days or oral consumption in the drinking water for 5 days before 15 minutes of warm ischemia and 24 hours of reperfusion. After EGCG administration, total baseline hepatic fat content decreased from baseline. Palmitic acid and linoleic acid levels also were reduced substantially in all ECGC-treated animals before I/R. Alanine aminotransferase (ALT) levels decreased in all EGCG-treated animals compared with control animals after I/R. Histologic analysis demonstrated an average decrease of 65% necrosis after EGCG administration. EGCG administration also increased resting hepatic energy stores as determined by an increase in cellular adenosine triphosphate (ATP) with a concomitant decrease in uncoupling protein 2 (UCP2) before I/R. Finally, there was an increased level of glutathione (GSH) in the EGCG-treated mice compared with the vehicle-treated mice both at baseline and after I/R. In conclusion, taken together, this study demonstrates that treatment with ECGC by either oral or ip administration, significantly protects the liver after I/R, possibly by reducing hepatic fat content, increasing hepatic energy status, and functioning as an antioxidant. (Liver Transpl 2005;11:298,308.) [source] The polyphenol epigallocatechin-3-gallate affects lipid rafts to block activation of the c-Met receptor in prostate cancer cellsMOLECULAR CARCINOGENESIS, Issue 8 2010Damian Duhon Abstract The HGF/c-Met pathway is an important regulator of signaling pathways responsible for invasion and metastasis of most human cancers, including prostate cancer. Exposure of DU145 prostate tumor cells to HGF stimulates the PI3-kinase and MAPK pathways, leading to increased scattering, motility, and invasion, which was prevented by the addition of EGCG. EGCG acted at the level of preventing phosphorylation of tyrosines 1234/1235 in the kinase domain of the c-Met receptor without effecting dimerization. HGF-induced changes were independent of the formation of reactive oxygen species, suggesting that EGCG functioned independent of its antioxidant ability. ECG, another tea polyphenol, was as effective as EGCG, while EGC and EC were less effective. EGCG added up to 4,h after the addition of HGF still blocked cell scattering and reduced the HGF-induced phosphorylation of c-Met, Akt, and Erk, suggesting that EGCG could act both by preventing activation of c-Met by HGF and by attenuating the activity of pathways already induced by HGF. HGF did not activate the MAPK and PI3-K pathways in cells treated with methyl-,-cyclodextrin (mCD) to remove cholesterol. Furthermore, subcellular fractionation approaches demonstrated that only phosphorylated c-Met accumulated in Triton X-100 membrane insoluble fractions, supporting a role for lipid rafts in regulating c-Met signaling. Finally, EGCG treatment inhibited DiIC16 incorporation into membrane lipid ordered domains, and cholesterol partially inhibited the EGCG effects on signaling. Together, these results suggest that green tea polyphenols with the R1 galloyl group prevent activation of the c-Met receptor by altering the structure or function of lipid rafts. © 2010 Wiley-Liss, Inc. [source] Fyn is a novel target of (,)-epigallocatechin gallate in the inhibition of JB6 Cl41 cell transformation,MOLECULAR CARCINOGENESIS, Issue 3 2008Zhiwei He Abstract The cancer preventive action of (,)-epigallocatechin gallate (EGCG), found in green tea, is strongly supported by epidemiology and laboratory research data. However, the mechanism by which EGCG inhibits carcinogenesis and cell transformation is not clear. In this study, we report that EGCG suppressed epidermal growth factor (EGF)-induced cell transformation in JB6 cells. We also found that EGCG inhibited EGF-induced Fyn kinase activity and phosphorylation in vitro and in vivo. Fyn was implicated in the process because EGF-induced JB6 cell transformation was inhibited by small interfering RNA (siRNA)-Fyn-JB6 cells. With an in vitro protein-binding assay, we found that EGCG directly bound with the GST-Fyn-SH2 domain but not the GST-Fyn-SH3 domain. The Kd value for EGCG binding to the Fyn SH2 domain was 0.367,±,0.122 µM and Bmax was 1.35,±,0.128 nmol/mg. Compared with control JB6 Cl41 cells, EGF-induced phosphorylation of p38 MAP kinase (p38 MAPK) (Thr180/Tyr182), ATF-2 (Thr71) and signal transducer and activator of transcription 1 (STAT1) (Thr727) was decreased in siRNA-Fyn-JB6 cells. EGCG could inhibit the phosphorylation of p38 MAPK, ATF-2, and STAT1. The DNA binding ability of AP-1, STAT1, and ATF-2 was also decreased in siRNA-Fyn-JB6 cells. Overall, these results demonstrated that EGCG interacted with Fyn and inhibited Fyn kinase activity and thereby regulated EGF-induced cell transformation. Inhibition of Fyn kinase activity is a novel and important mechanism that may be involved in EGCG-induced inhibition of cell transformation. © 2007 Wiley-Liss, Inc. [source] Structure-activity relationship of flavonoids for inhibition of epidermal growth factor-induced transformation of JB6 Cl 41 cellsMOLECULAR CARCINOGENESIS, Issue 6 2007Daisuke Ichimatsu Abstract We found that quercetin, myricetin, quercetagetin, fisetin, (,)-epigallocatechin gallate (EGCG), and theaflavins, among 24 flavonoids examined, markedly inhibited epidermal growth factor (EGF)-induced cell transformation of mouse epidermal JB6 Cl 41 cells. The six flavonoids suppressed the EGF-induced activation of activator protein 1 (AP-1). In addition, myricetin, quercetagetin, EGCG, and theaflavins directly inhibited EGF-induced phosphatidylinositol 3-kinase (PI3K) activation. The important structural features of flavonoids for cell transformation-inhibitory activity are 3,- and 4,-OH on the B-ring, 3-OH on the C-ring, C2C3 double bond in the C-ring, and the phenylchromone (C6C5C6) skeleton in the flavonols, and the galloyl group in EGCG and theaflavins. Our results provide new insight into possible mechanisms of the anti-carcinogenic effects of flavonoids, and could help to provide a basis for the design of novel cancer chemopreventive agents. © 2007 Wiley-Liss, Inc. [source] Molecular targets for the cancer preventive activity of tea polyphenolsMOLECULAR CARCINOGENESIS, Issue 6 2006Chung S. Yang Abstract Inhibition of carcinogenesis by tea and tea polyphenols has been demonstrated in many animal models. The mechanisms of action have been extensively investigated mostly in cell culture systems with (-)-epigallocatechin-3-gallate (EGCG), the most active and major polyphenolic compound from green tea. However, the mechanisms of cancer preventive activity by tea and tea polyphenols are not clearly understood. This article discusses some of the reported mechanisms and possible targets for the action of EGCG. The difficulties and major issues in extrapolating data from studies in cancer cell lines to cancer prevention mechanisms are discussed. Activities observed in cell culture with high concentrations of EGCG may not be relevant because of the limited systemic bioavailability of EGCG. In addition, possible artifacts due to the auto-oxidation of EGCG may complicate this issue. Some recent studies revealed high-affinity EGCG binding proteins as possible direct targets for the action of EGCG. Validating the related cancer preventive mechanisms found in in vitro studies in animal models and human samples would be exciting. © 2006 Wiley-Liss, Inc. [source] Cover Picture , Mol.MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 9 2009Nutr. Regular issues provide a wide range of research and review articles covering all aspects of Molecular Nutrition & Food Research. Selected topics of issue 9 are: Efficacy of isoflavones in relieving vasomotor menopausal symptoms , a systematic review. Aromatic hydroxylation is a major metabolic pathway of the mycotoxin zearalenone in vitro HOP BITTER ACIDS EFFICIENTLY BLOCK INFLAMMATION INDEPENDENT OF GR,, PPAR, OR PPAR, EGCG inhibits protein synthesis, lipogenesis and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cells [source] EGCG inhibits protein synthesis, lipogenesis, and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cellsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 9 2009Chi-Hung Huang Abstract In the previous studies, (,)-epigallocatechin-3-gallate (EGCG) has been shown to have anticarcinogenic effects via modulation in protein expression of p53. Using p53 positive Hep G2 and p53 negative Hep 3B cells, we found that treatment of EGCG resulted in dose-dependent inhibition of cellular proliferation, which suggests that the interaction of EGCG with p53 may not fully explain its inhibitory effect on proliferation. Caloric restriction (CR) reduces the incidence and progression of spontaneous and induced tumors in laboratory rodents. EGCG has multiple beneficial activities similar to those associated with CR. One key enzyme thought to be activated during CR is AMP-activated kinase (AMPK), a sensor of cellular energy levels. Here, we showed that EGCG activated AMPK in both p53 positive and negative human hepatoma cells. The activation of AMPK suppressed downstream substrates, such as mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and a general decrease in mRNA translation. Moreover, EGCG activated AMPK decreases the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). Interestingly, the decision between apoptosis and growth arrest following AMPK activation is greatly influenced by p53 status. In p53 positive Hep G2 cells, EGCG blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21 expression. However, EGCG inducted apoptosis in p53 negative Hep 3B cells. Based on these results, we have demonstrated that EGCG has a potential to be a chemoprevention and anti-lipogenesis agent for human hepatoma cells. [source] The modulation of endothelial cell gene expression by green tea polyphenol-EGCGMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 10 2008Liping Liu Abstract Human and animal studies have shown that green tea consumption is associated with a reduced risk of some cancers. This has been attributed to its polyphenol components, in particular (,)-epigallocatechin gallate (EGCG). In addition to be a cancer chemopreventive agent, EGCG inhibits angiogenesis, thus reducing tumor growth and metastasis. We tested EGCG modulation on the gene expression profile of endothelial cells stimulated by VEGF using Affymetrix microarrays. A total of 421 genes were up-regulated and 72 genes were down-regulated at the false discovery rate of 5% by VEGF, EGCG, and EGCG pretreatment followed by VEGF stimulation. The changes in the expression of several pivotal genes were validated by real-time PCR. Furthermore, we have identified two signaling pathways (Wnt and Id) involved in cell proliferation were inhibited by EGCG treatment, suggesting the negative regulation of EGCG on cell proliferation. Our results also indicate that the antiangiogenesis effect of EGCG is partially mediated through its broad inhibition on endothelial cell proliferation. Our data further support earlier observations that the anticancer effect of EGCG is mediated through changes in the expression of genes that are associated with cell proliferation. [source] Epigallocatechin gallate (EGCG) attenuates high glucose-induced insulin signaling blockade in human hepG2 hepatoma cellsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 8 2008Chih-Li Lin Abstract Insulin resistance is the primary characteristic of type 2 diabetes which as a result of insulin signaling defects. It has been suggested that the tea polyphenol (,)-epigallocatechin-3-gallate (EGCG) displays some antidiabetic effects, but the mechanism for EGCG insulin-enhancing effects is incompletely understood. In the present study, the investigations of EGCG on insulin signaling are performed in insulin-responsive human HepG2 cells cotreated with high glucose. We found that the high glucose condition causes significant increasing Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1), leading to reduce insulin-stimulated phosphorylation of Akt. As the results, the insulin metabolic effects of glycogen synthesis and glucose uptake are inhibited by high glucose. However, the treatment of EGCG improves insulin-stimulated downsignaling by reducing IRS-1 Ser307 phosphorylation. Furthermore, we also demonstrated these EGCG effects are essential depends on the 5,-AMP-activated protein kinase (AMPK) activation. Together, our data suggest a putative link between high glucose and insulin resistance in HepG2 cells, and the EGCG treatment attenuates insulin signaling blockade by reducing IRS-1 Ser307 phosphorylation through the AMPK activation pathway. [source] Free Zn2+ enhances inhibitory effects of EGCG on the growth of PC-3 cellsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 4 2008Shi-li Sun Abstract Epigallocatechin-3-gallate (EGCG), a major component of green tea, has both preventive and therapeutic beneficial actions in prostate cancer. In the present study, we compared the growth inhibitory effects and the antioxidant and ability to modify cell membrane permeation of zinc-EGCG complex and Zn2+/EGCG mixture on androgen-insensitive prostate cancer (PC-3) cells. It was noted that free Zn2+ enhanced the growth inhibitory effects of EGCG on PC-3 cells at 160 ,mol/L concentration, whereas zinc-EGCG complex was ineffective. EGCG showed potent free radical scavenging ability in the presence of Zn2+. EGCG in the presence of Zn2+ was more effective than EGCG alone in enhancing the permeability of the cell membrane, whereas zinc-EGCG complex had no effect on PC-3 cell membrane permeability. These results indicate that though Zn2+ enhanced the action of EGCG on PC-3 cells, zinc-EGCG complex is highly unlikely to be formed in the presence of Zn2+ and EGCG to explain the potentiating action of Zn2+ on the growth inhibitory property of EGCG on PC-3 cells. [source] Mechanisms and Effects of Green Tea on Cardiovascular HealthNUTRITION REVIEWS, Issue 8 2007Arpita Basu PhD Green tea, rich in antioxidant and anti-inflammatory catechins, especially epigallocatechin gallate (EGCG), has been shown to reduce surrogate markers of atherosclerosis and lipid peroxidation, particularly LDL oxidation and malondialdehyde concentrations, in several in vitro, animal, and limited clinical studies. Epidemiological observations in Southeast Asian countries indicate an inverse correlation exists between habitual consumption of green tea beverages and the incidence of cardiovascular events. A few short-term clinical studies have reported its effects in attenuating biomarkers of oxidative stress and inflammation among smokers, and an ability to decrease postprandial lipemia in hypercholesterolemic subjects has also been suggested. However, further investigations are needed to confirm the potential role of green tea beverages and the safety of green tea supplements in reducing body fat, as well as other biomarkers of cardiovascular disease risks. [source] Green Tea Polyphenols and Cancer Chemoprevention: Multiple Mechanisms and Endpoints for Phase II TrialsNUTRITION REVIEWS, Issue 5 2004M.P.H., Susan B. Moyers Ph.D. Among the numerous polyphenols isolated from green tea, the catechin EGCG predominates and is the target of anticancer research. But studies suggest that EGCG and other catechins are poorly absorbed and undergo substantial biotransformation to species that include glucuronides, sulfates, and methylated compounds. Numerous studies relate the antioxidant properties of the catechins with anticancer effects, but recent research proposes other mechanisms of action, including those involving methyl transfers that are subject to allelic variability in the enzyme catechol O-methyl transferase. However, preclinical research is promising and EGCG appears to be ready for further study in phase II and III trials. [source] Epigallocatechin-3-Gallate Inhibits Photocarcinogenesis Through Inhibition of Angiogenic Factors and Activation of CD8+ T Cells in TumorsPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2005Sudheer K. Mantena ABSTRACT There has been considerable interest in the use of botanical supplements to protect skin from the adverse effects of solar UV radiation, including photocarcinogenesis. We and others have shown that topical application of (,)-epigallocatechin-3-gallate (EGCG) from green tea prevents photocarcinogenesis in mice; however, the chemopreventive mechanism of EGCG in an in vivo tumor model is not clearly understood. In this study, UV-B-induced skin tumors with and without treatment of EGCG (,1 mg/cm2) and age-matched skin biopsies from SKH-1 hairless mice were used to identify potential molecular targets of skin cancer prevention by EGCG. These biopsies were analyzed for various biomarkers of angiogenesis and antitumor immune response using immunostaining, Western blotting and gelatinolytic zymography. We report that compared to non-EGCG-treated tumors, topical application of EGCG in UV-induced tumors resulted in inhibition of protein expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, which play crucial roles in tumor growth and metastasis. In contrast, tissue inhibitor of MMP-1 (TIMP-1), which inhibits MMP activity, was increased in tumors. With respect to the tumor vasculature, EGCG decreased the expression of CD31, a cell surface marker of vascular endothelial cells, and inhibited the expression of vascular endothelial growth factor in tumors, which are essential for angiogenesis. EGCG inhibited proliferating cell nuclear antigen in UV-B-induced tumors as well. Additionally, higher numbers of cytotoxic T lymphocytes (CD8+ T cells) were detected in EGCG-treated tumors compared with non-EGCG-treated tumors. Together, these in vivo tumor data suggested that inhibition of photocarcinogenesis in mice by EGCG is associated with inhibition of angiogenic factors and induction of antitumor immune reactivity. [source] Modification of gamma-radiation response in mice by green tea polyphenolsPHYTOTHERAPY RESEARCH, Issue 10 2008Hae June Lee Abstract In this study we evaluated the effect of water extracts of green tea (GT) and mixtures of green tea polyphenols (GTPs), epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC) and epicatechin (EC) on jejunal crypt survival, endogenous spleen colony formation, and apoptosis in jejunal crypt cells of mice irradiated with gamma-ray. The radioprotective effect of green tea was compared with the effect of diethyldithiocarbamate (DDC). Jejunal crypts were protected by pretreatment of GT and ECG. Administration of GT, GTPs and EC prior to irradiation resulted in an increase in the formation of endogenous spleen colonies. The frequency of apoptosis in crypt cells was also reduced by pretreatment of GT, GTPs, EGCG, ECG and EGC. In the experiment on the effect of catechins, the effects were partly contradicted in irradiated mice. The rank order of activity was ECG > EGC > EGCG > EC on intestinal crypt survival assay, EC > EGC > ECG > EGCG on the spleen colony formation assay, EGCG > EGC > EC > ECG on inhibiting the death of cells caused by apoptosis. The results indicate that GT and GTPs may have a major radioprotective effect. Each one of the catechins was a much less effective radioprotector, suggesting that total extract or a mixture of GTPs may be more effective than individual catechins. Copyright © 2008 John Wiley & Sons, Ltd. [source] Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cellsPHYTOTHERAPY RESEARCH, Issue 5 2008Sang Il Lee Abstract Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas l -theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S -adenosyl- l -methionine, N -acetyl- l -cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage. Copyright © 2008 John Wiley & Sons, Ltd. [source] Protective effect of green tea polyphenol (-)-epigallocatechin gallate and other antioxidants on lipid peroxidation in gerbil brain homogenatesPHYTOTHERAPY RESEARCH, Issue 3 2003Seong-Ryong Lee Abstract The aim of this study was to compare the protective effects of green tea polyphenol (-)-epigallocatechin gallate (EGCG) and other well-known antioxidants on the lipid peroxidation in gerbil brain homogenates. Oxidative stress was induced by H2O2 (10 mM) or ferrous ammonium sulfate (5 µM) and lipid peroxidation was studied. Hydrogen peroxide and ferrous ions are capable of oxidizing a wide range of substrates and causing biological damage. The reaction, referred to as the Fenton process, is complex and can generate both hydroxyl radicals and higher oxidation states of the iron. Thiobarbituric acid-reactive substances (TBA-RS) were used as a marker of lipid peroxidation. EGCG, trolox, lipoic acid, and melatonin reduced H2O2 - or ferrous ion-induced lipid peroxidation in a concentration-dependant manner. In reducing the H2O2 -induced lipid peroxidation, IC50 values of antioxidants were as follows: EGCG (0.66 µM), trolox (37.08 µM), lipoic acid (7.88 mM), and melatonin (19.11 mM). In reducing the ferrous ion-induced lipid peroxidation, IC50 values of antioxidants were as follows: EGCG (3.32 µM), trolox (75.65 µM), lipoic acid (7.63 mM), and melatonin (15.48 mM). Under the in vitro conditions of this experiment, EGCG was the most potent antioxidant in inhibiting H2O2 or ferrous ion-induced lipid peroxidation in the gerbil brain homogenates. Copyright © 2003 John Wiley & Sons, Ltd. [source] Green tea: Health benefits as cancer preventive for humansTHE CHEMICAL RECORD, Issue 3 2005Hirota Fujiki Abstract Green tea is an acknowledged cancer preventive in Japan. The aim of this review article is to develop the concept of cancer prevention with green tea beverage for humans, which has largely been our exclusive research territory. This paper briefly reviews several topics, beginning with the introduction of our initial work on penta- O -galloyl-,-D-glucose and (,)-epigallocatechin gallate (EGCG), the main constituent of green tea extract. The mechanisms of EGCG action, particularly the reduction of TNF-, are discussed, and we show how use of 3H-EGCG revealed a wide range of target organs for cancer prevention. The results of an epidemiological study in Saitama Prefecture allowed us to determine the cancer preventive amount of green tea,10 Japanese-size cups per day, about 2.5,g green tea extract,which made it possible for us to introduce the two-stage strategy of cancer prevention with green tea. The first stage is the delay of cancer onset for the general population. The second stage is the prevention of recurrence of cancer for patients following cancer treatment. Combination cancer prevention with green tea and cancer preventive drugs is proving especially beneficial for Japanese, who drink green tea every day. And finally, the stimulating comments of Prof. Jim Watson have encouraged green tea scientists. © 2005 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 5: 119,132; 2005: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20039 [source] | |||||||||||||||||||||||||||||||