Reduces oxidative DNA damage, lipid peroxidation and free radical generation Anti-inflammatory

Green Tea 95% Extract (standardized to 95% polyphenols)
Epigallocatchin Gallate (EGCG) (standardized to 45% EGCG)


Green Tea
Study on Ability of Extraction Alcohol from Eight Kinds Chinese Traditional Medicine in Inhibiting Two Free Radicals
Objective: To study on the ability of extraction alcohol from eight kinds Chinese traditional medicine in inhibiting two free radicals, and to provide the solid foundation for the development of anti-old medicine. Methods: Pyrogollol self-oxidation was employed to measure the ability of extraction alcohol from eight kinds Chinese traditional medicine in inhibiting two free radicals to super-oxide radical. Fonten Reaction was employed to test the ability of inhibition of extraction alcohol to hydroxyl radical.
Results: (1)The ability of extraction alcohol from eight kinds Chinese traditional medicine in inhibiting two free radicals to super-oxide radical could be ranked as. -fructus schizandrae>green tea> radix glycy:rrhizae >radix astragali>rhizome ligusitc>radix et rhizome rehmanniae >radix codonopsitis>radix salviae miltiorrhize. (2)The ability of extraction alcohol from eight kinds Chinese traditional medicine in inhibiting two free radicals to hydroxyl radical could be ranked as:green tea>fructus schizandrae>radix glycyrrhizae>rhizome ligusite>radix et rhizome rehmanniae>radix codonopsitis >radix salviae miltiorrhize>fructus schizandrae. Conclusions: Extraction alcohol from eight kinds Chinese traditional medicine possess the ability of clearance to both super-oxide radical and hydroxyl radical.
WAN Hong. Zhong Guo Wu Zhen Xue Za Zhi. 2008; 8(32): 7821-7823.

EGCG & Cancer
Epidemiological evidence suggests tea (Camellia sinensis L.) has chemopreventive effects against various tumours. 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 tumourigenesis 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 tumours per tumour-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 oestrogen 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 tumourigenesis 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
Kavanagh, K.T., Hafer, L.J., Kim, D. W., Mann, K.K., Sherr, D.H., Rogers, A.E., Sonenshein, G.E. Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture. Journal of Cellular Biochemistry. Vol 82 Issue 3, Pp. 387-98. DOI:10.1002/jcb.1164

EGCG & Metastasis
Flavanol (-)epigallocatechin-3-gallate is shown to be a potent natural inhibitor of leukocyte elastase that may be used to reduce elastase-mediated progression to emphysema and tumour invasion. This phyto-factor, abundant in green tea, exerts a dose-dependent, noncompetitive inhibition of leukocyte elastase at a noncytotoxic concentration and is effective in neutrophil culture. This inhibition shows an IC50 of 0.4 ÁM, 30 times higher than the {alpha}1-protease inhibitor but lower than other known natural and synthetic elastase inhibitors. The flavanol inhibits leukocyte elastase at concentrations of 50, 150, and 2500 times lower than that effective on gelatinases (MMP-2 and MMP-9), thrombin, and cathepsin G, respectively, and also blocks elastase-mediated activation of MMP-9.
Sartor, L., Pezzato,E. & Garbisa, S. (-)Epigallocatechin-3-gallate inhibits leukocyte elastase: potential of the phyto-factor in hindering inflammation, emphysema, and invasion. Journal of Leukocyte Biology. 2002;71:Pp.73-79.

Epicatechin gallate (ECG) and catechin gallate (CG) are superior to epigallocatechin gallate (ECGC) in growth suppression and anti-inflammatory activities in pancreatic tumour cells

Green tea catechins are considered as possible cancer preventive agents for several cancer types but little is known regarding their effects on pancreatic cancer cells. The best studied catechin and the major polyphenol present in green tea is epigallocatechin gallate (EGCG). In the present study, we investigated the in vitro anti-tumoral properties of EGCG on human PDAC (pancreatic ductal adenocarcinoma) cells PancTu-I, Panc1, Panc89 and BxPC3 in comparison with the effects of two minor components of green tea catechins catechin gallate (CG) and epicatechin gallate (ECG). We found that all three catechins inhibited proliferation of PDAC cells in a dose- and time-dependent manner. Interestingly, CG and ECG exerted much stronger anti-proliferative effects than EGCG. Western blot analyses performed with PancTu-I cells revealed catechin-mediated modulation of cell cycle regulatory proteins (cyclins, cyclin-dependent kinases [CDK], CDK inhibitors). Again, these effects were clearly more pronounced in CG or ECG than in EGCG treated cells. Importantly, catechins, in particular ECG, inhibited TNFα-induced activation of NF-κB and consequently secretion of pro-inflammatory and invasion promoting proteins like IL-8 and uPA. Overall, our data show that green tea catechins ECG and CG exhibit potent and much stronger anti-proliferative and anti-inflammatory activities on PDAC cells than the most studied catechin EGCG.
Kürbitz C, Heise D, Redmer T, Goumas F, et al. Cancer Science. Online publication Jan 2011. DOI: 10.1111/j.1349-7006.2011.01870.x

The green tea catechins, (-)-Epigallocatechin-3-gallate (EGCG) and (-)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells.
The hepatocyte growth factor (HGF) receptor, Met, is a strong prognostic indicator of breast cancer patient outcome and survival, suggesting that therapies targeting Met may have beneficial outcomes in the clinic. (-)-Epigallocatechin-3-gallate (EGCG), a catechin found in green tea, has been recognized as a potential therapeutic agent. We assessed the ability of EGCG to inhibit HGF signaling in the immortalized, nontumorigenic breast cell line, MCF10A, and the invasive breast carcinoma cell line, MDA-MB-231. HGF treatment in both cell lines induced rapid, sustained activation of Met, ERK and AKT. Pretreatment of cells with concentrations of EGCG as low as 0.3 muM inhibited HGF-induced Met phosphorylation and downstream activation of AKT and ERK. Treatment with 5.0 muM EGCG blocked the ability of HGF to induce cell motility and invasion. We assessed the ability of alternative green tea catechins to inhibit HGF-induced signaling and motility. (-)-Epicatechin-3-gallate (ECG) functioned similar to EGCG by completely blocking HGF-induced signaling as low as 0.6 muM and motility at 5 muM in MCF10A cells; whereas, (-)-epicatechin (EC) was unable to inhibit HGF-induced events at any concentration tested. (-)-Epigallocatechin (EGC), however, completely repressed HGF-induced AKT and ERK phosphorylation at concentrations of 10 and 20 muM, but was incapable of blocking Met activation. Despite these observations, EGC did inhibit HGF-induced motility in MCF10A cells at 10 muM. These observations suggest that the R1 galloyl and the R2 hydroxyl groups are important in mediating the green tea catechins' inhibitory effect towards HGF/Met signaling. These combined in vitro studies reveal the possible benefits of green tea polyphenols as cancer therapeutic agents to inhibit Met signaling and potentially block invasive cancer growth.
Bigelow RLH, & Cardelli JA. Oncogene (2006) 25, 1922–1930. doi:10.1038/sj.onc.1209227;

Mechanisms of Growth Inhibition of Human Lung Cancer Cell Line, PC-9, by Tea Polyphenols
(–)-Epigallocatechin gallate (EGCG), the main constituent of green tea, and green tea extract show growth inhibition of various cancer cell lines, such as lung, mammary, and stomach. We studied how tea polyphenols induce growth inhibition of cancer cells. Since green tea extract contains various tea polyphenols, such as EGCG, (–)-epigallocatechin (EGC), (–)-epicatechin gallate (ECG), and (–)-epicatechin (EC), the inhibitory potential of each tea polyphenol on the growth of a human lung cancer cell line, PC-9 cells, was first examined. EGC and ECG inhibited the growth of PC-9 cells as potently as did EGCG, but EC did not show significant growth inhibition. The mechanism of growth inhibition by EGCG was studied in relation to cell cycle regulation. Flow cytometric analysis revealed that treatment with 50 μM and 100 μM EGCG increased the percentages of cells in the G2-M phase from 13.8% to 15.6% and 24.1%, respectively. The DNA histogram after treatment with 100 μM EGCG was similar to that after treatment with genistein, suggesting that EGCG induces G2-M arrest in PC-9 cells. Moreover, we found by microautoradiography that [3H]EGCG was incorporated into the cytosol, as well as the nuclei. These results provide new insights into the mechanisms of action of EGCG and green tea extract as cancer-preventive agents in humans.
Okabe S, Suganuma M, Hayashi M, et al. Cancer Science. Volume 88, Issue 7, pages 639–643, July 1997. DOI: 10.1111/j.1349-7006.1997.tb00431.x

Selective inhibition of ADAMTS-1, -4 and -5 by catechin gallate esters
Three mammalian ADAMTS enzymes, ADAMTS-1, -4 and -5, are known to cleave aggrecan at certain glutamyl bonds and are considered to be largely responsible for cartilage aggrecan catabolism observed during the development of arthritis. We have previously reported that certain catechins, polyphenolic compounds found in highest concentration in green tea (Camellia sinensis), are capable of inhibiting cartilage aggrecan breakdown in an in vitro model of cartilage degradation. We have now cloned and expressed recombinant human ADAMTS-1, -4 and -5 and report here that the catechin gallate esters found in green tea potently inhibit the aggrecan-degrading activity of these enzymes, with submicromolar IC50 values. Moreover, the concentration needed for total inhibition of these members of the ADAMTS group is approximately two orders of magnitude lower than that which is needed to partially inhibit collagenase or ADAM-10 activity. Catechin gallate esters therefore provide selective inhibition of certain members of the ADAMTS group of enzymes and could constitute an important nutritional aid in the prevention of arthritis as well as being part of an effective therapy in the treatment of joint disease and other pathologies involving the action of these enzymes.
Vankemmelbeke MN, Jones GC, Fowles C, et al. European Journal of Biochemistry. Volume 270, Issue 11, Pp 2394–403, June 2003. DOI: 10.1046/j.1432-1033.2003.03607.x

Comparison of antioxidant activity and bioavailability of tea epicatechins with their epimers
GTE–epimer mixture namely (−)-gallocatechin gallate (GCG), (−)-catechin gallate (CG), (−)-gallocatechin (GC) and (−)-catechin (C) led to increase in total plasma antioxidant capacity.
Xu JZ, Yeung SYV, Chang Q, et al. British Journal of Nutrition (2004), 91 Pp. 873-81. DOI: 10.1079/BJN20041132

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