cancer-prevention

Author: Michael A. Moses and Ellen C. Henry and William A. Ricke and Thomas A. Gasiewicz

(−)-Epigallocatechin gallate (EGCG), a major tea polyphenol, elicits anticancer effects. However, the mechanism of action is not fully understood. Our laboratory previously showed that EGCG inhibits heat shock protein 90 (HSP90). We used nontumorigenic (NT), tumorigenic, and metastatic cancer cells from a novel human prostate cancer progression model to test the hypotheses that certain stages are more or less sensitive to EGCG and that sensitivity is related to HSP90 inhibition. Treatment of cells with EGCG, novobiocin, or 17-AAG resulted in more potent cytotoxic effects on tumorigenic and metastatic cells than NT cells. When tumorigenic or metastatic cells were grown in vivo, mice supplemented with 0.06% EGCG in drinking water developed significantly smaller tumors than untreated mice. Furthermore, EGCG prevented malignant transformation in vivo using the full prostate cancer model. To elucidate the mechanism of EGCG action, we performed binding assays with EGCG-Sepharose, a C-terminal HSP90 antibody, and HSP90 mutants. These experiments revealed that EGCG-Sepharose bound more HSP90 from metastatic cells compared with NT cells and binding occurred through the HSP90 C-terminus. In addition, EGCG bound HSP90 mutants that mimic both complexed and uncomplexed HSP90. Consistent with HSP90 inhibitory activity, EGCG, novobiocin, and 17-AAG induced changes in HSP90-client proteins in NT cells and larger differences in metastatic cells. These data suggest that EGCG may be efficacious for the treatment of prostate cancer because it preferentially targets cancer cells and inhibits a molecular chaperone supportive of the malignant phenotype. 

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Author: Binbin Chen and Guangyi Liu and Peimei Zou and Xing Li and Qiufa Hao and Bei Jiang and Xiangdong Yang and Zhao Hu

Cisplatin (CP)-induced nephrotoxicity hampers its application in clinic. Green tea, particularly its predominant polyphenolic constituent epigallocatechin-3-gallate (EGCG), possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. The present study was designed to investigate the protective effects of EGCG against CP-induced nephrotoxicity in mice. Male C57/BL6 mice in different groups received single injection of CP (20 mg/kg) and EGCG (100 mg/kg) in various sets and kidney tissues and blood were collected after killing. Then, samples were used for biochemical and immunohistochemical assay. Our results showed EGCG decreased biochemical factors and immunohistochemical damage induced by CP. Besides, expression of phosphorylated-extracellular signal-regulated kinase (p-ERK), glucose-regulated protein 78 (GRP78), caspase-12, and apoptosis of kidney were decreased by EGCG via inhibition of endoplasmic reticulum (ER) stress-induced apoptosis.

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Author: Anja Mähler and Jochen Steiniger and Markus Bock and Lars Klug and Nadine Parreidt and Mario Lorenz and Benno F Zimmermann and Alexander Krannich and Friedemann Paul and Michael Boschmann

Background: Muscle weakness and fatigue are common symptoms in multiple sclerosis (MS). Green tea catechins such as (−)epigallocatechin-3-gallate (EGCG) are known to improve energy metabolism at rest and during exercise. Objective: We tested the hypothesis that EGCG improves energy metabolism and substrate utilization in patients with MS. Design: Eighteen patients (8 men) with relapsing-remitting MS (expanded disability status scale score <4.5, all receiving glatiramer acetate) participated in this randomized, double-blind, placebo-controlled, crossover trial at a clinical research center. All patients received EGCG (600 mg/d) and placebo over 12 wk (4-wk washout in between). After each intervention, fasting and postprandial energy expenditure (EE), as well as fat oxidation (FAOx) and carbohydrate oxidation (CHOx) rates, were measured either at rest or during 40 min of exercise (0.5 W/kg). At rest, blood samples and microdialysates from adipose tissue and skeletal muscle were also taken. Results: At rest, postprandial EE and CHOx, as well as adipose tissue perfusion and glucose supply, were significantly lower in men but higher in women receiving EGCG compared with placebo. During exercise, postprandial EE was lower after EGCG than after placebo, indicating an increased working efficiency (men > women). After placebo, exercise EE was mainly fueled by FAOx in both men and women. After EGCG, there was a shift to a higher and more stable CHOx during exercise in men but not in women. Conclusions: Our data indicate that EGCG given to patients with MS over 12 wk improves muscle metabolism during moderate exercise to a greater extent in men than in women, possibly because of sex-specific effects on autonomic and endocrine control. 

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Effects of dietary supplementation with green tea polyphenols on digestion and meat quality in lambs infected with Haemonchus contortus

Author: Zhong RZ and Li HY and Fang Y and Sun HX and Zhou DW

Ujumqin sheep are susceptible to infection by the gastrointestinal nematode Haemonchus contortus, which reduces productivity and total meat yield in sheep. Thus, the effects of green tea polyphenol (GTP) supplements (0, 2, 4, or 6 g of GTP/kg feed) on dietary nutrient digestibility and meat quality in lambs infected with H. contortus were examined; control lambs were not infected. H. contortusinfections did not affect digestion but the apparent digestibilities of nutrients were decreased by dietary 2 g of GTP/kg feed supplementation. There was an interaction between treatment and sampling time on plasma total protein, urea nitrogen, and amino acid concentrations. The antioxidant activity and meat color of INFGTP0 lambs decreased. In conclusion, H. contortus infections in lambs decreased meat quality, but appropriate levels of dietary GTP supplementation diminished these negative effects though lower dose of GTP supplement showed negative effects on digestion.

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Author: Haskell CF, and Kennedy DO, and Milne AL, and Wesnes KA, and Scholey AB

L-Theanine is an amino acid found naturally in tea. Despite the common consumption of l-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of l-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were co-monitored. l-Theanine increased ‘headache’ ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported ‘mental fatigue’. In addition to improving RVIP accuracy and ‘mental fatigue’ ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. ‘Headache’ and ‘tired’ ratings were reduced and ‘alert’ ratings increased. There was also a significant positive caffeine × l-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing l-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.

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Author: Yohei Mineharu, and Akio Koizumi, and Yasuhiko Wada, and Hiroyasu Iso, and Yoshiyuki Watanabe, and Chigusa Date, and Akio Yamamoto, and Shogo Kikuchi, and Yutaka Inaba, and Hideaki Toyoshima, and Takaaki Kondo, and Akiko Tamakoshi

Background: The effects of coffee and green, black and oolong teas and caffeine intake on cardiovascular disease (CVD) mortality have not been well defined in Asian countries. Methods: To examine the relationship between consumption of these beverages and risk of mortality from CVD, we prospectively followed 76,979 individuals aged 40-79 y free of stroke, coronary heart disease (CHD), and cancer at entry. Daily consumption of beverages was assessed by questionnaires. Results: We documented 1362 deaths from strokes and 650 deaths from CHD after 1,010,787 person-years of follow-up. Compared with non-drinkers of coffee, the multivariable hazard ratios (HRs) and 95% confidence interval for those drinking 1-6 cups/wk, 1-2 cups/d and a ‰Ψ3 cups/d were 0.78 (0.50-1.20), 0.67 (0.47-0.96) and 0.45 (0.17-0.87) for strokes among men (p=0.009 for trend). Compared with non-drinkers of green tea, the multivariable HRs for those drinking 1-6 cups/wk, 1-2 cups/d, 3-5 cups/d and a ‰Ψ6 cups/d were 0.34 (0.06-1.75), 0.28 (0.07-1.11), 0.39 (0.18-0.85), and 0.42 (0.17-0.88) for CHD among women (p=0.038 for trend). As for oolong tea, the multivariable HRs of those drinking 1-6 cups/wk and a ‰Ψ1 cups/d were 1.00 (0.65-1.55) and 0.39 (0.17-0.88) for total CVD among men (p=0.049 for trend). Risk reduction for total CVD across categories of caffeine intake was most prominently observed in the second highest quintile with a 38% lower risk among men and 22% among women. Conclusions: Consumption of coffee, green tea and oolong tea and total caffeine intake was associated with a reduced risk of mortality from CVD.

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Author: Kim Zarse and Saskia Jabin and Michael Ristow

Author: Tsuge H, and Sano S, and Hayakawa T, and Kakuda T, and Unno T

Author: Anna C Nobre PhD and Anling Rao PhD and Gail N Owen PhD

Tea is the most widely consumed beverage in the world after water. Tea is known to be a rich source of flavonoid antioxidants. However tea also contains a unique amino acid, L-theanine that may modulate aspects of brain function in humans. Evidence from human electroencephalograph (EEG) studies show that it has a direct effect on the brain (Juneja et al. Trends in Food Science & Tech 1999;10;199-204). L-theanine significantly increases activity in the alpha frequency band which indicates that it relaxes the mind without inducing drowsiness. However, this effect has only been established at higher doses than that typically found in a cup of black tea (~20mg). The aim of the current research was to establish this effect at more realistic dietary levels. EEG was measured in healthy, young participants at baseline and 45, 60, 75, 90 and 105 minutes after ingestion of 50mg L-theanine (n=16) or placebo (n=19). Participants were resting with their eyes closed during EEG recording. There was a greater increase in alpha activity across time in the L-theanine condition (relative to placebo (p<0.05). A second study replicated this effect in participants engaged in passive activity. These data indicate that L-theanine, at realistic dietary levels, has a significant effect on the general state of mental alertness or arousal. Furthermore, alpha activity is known to play an important role in critical aspects of attention, and further research is therefore focussed on understanding the effect of L-theanine on attentional processes.

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Author: Sanjay Gupta and Nihal Ahmad and Anna-Liisa Nieminen and Hasan Mukhtar

Prostate cancer (PCA) is the most prevalent cancer diagnosed and the second leading cause of cancer-related deaths among men in the United States. Descriptive epidemiological data suggest that androgens and environmental exposures play a key role in prostatic carcinogenesis. Since androgen action is intimately associated with proliferation and differentiation, at the time of clinical diagnosis in humans most PCA represent themselves as a mixture of androgen-sensitive and androgen-insensitive cells. Androgen-sensitive cells undergo rapid apoptosis upon androgen withdrawal. On the other hand, the androgen-insensitive cells do not undergo apoptosis upon androgen blocking, but maintain the molecular machinery of apoptosis. Thus, agents capable of inhibiting growth and/or inducing apoptosis in both androgen-sensitive and androgen-insensitive cells will be useful for the management of PCA. In the present study, we show that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent present in green tea, imparts antiproliferative effects against both androgen-sensitive and androgen-insensitive human PCA cells, and this effect is mediated by deregulation in cell cycle and induction of apoptosis. EGCG treatment was found to result in a dose-dependent inhibition of cell growth in both androgen-insensitive DU145 and androgen-sensitive LNCaP cells. In both the cell types, EGCG treatment also resulted in a dose-dependent G0/G1-phase arrest of the cell cycle as observed by DNA cell-cycle analysis. As evident by DNA ladder assay, confocal microscopy, and flow cytometry, the treatment of both DU145 and LNCaP cells with EGCG resulted in a dose-dependent apoptosis. Western blot analysis revealed that EGCG treatment resulted in (i) a dose-dependent increase of p53 in LNCaP cells (carrying wild-type p53), but not in DU145 cells (carrying mutant p53), and (ii) induction of cyclin kinase inhibitor WAF1/p21 in both cell types. These results suggest that EGCG negatively modulates PCA cell growth, by affecting mitogenesis as well as inducing apoptosis, in cell-type-specific manner which may be mediated by WAF1/p21-caused G0/G1-phase cell-cycle arrest, irrespective of the androgen association or p53 status of the cells.

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