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Green tea polyphenol epigallocatechin-3 gallate (EGCG) affects gene expression of breast cancer cells transformed by the carcinogen 7,12-dimethylbenz[a]anthracene.

Since the 1980s, the incidence of late-onset breast cancer has been increasing in the United States. Known risk factors, such as genetic modifications, have been estimated to account for approximately 5 to 10% of breast cancer cases, and these tend to be early onset. Thus, exposure to and bioaccumulation of ubiquitous environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs), have been proposed to play a role in this increased incidence. Treatment of female Sprague-Dawley rats with a single dose of the PAH 7,12-dimethylbenz[a]anthracene (DMBA) induces mammary tumors in approximately 90 to 95% of test animals. We showed previously that female rats treated with DMBA and given green tea as drinking fluid displayed significantly decreased mammary tumor burden and invasiveness and a significantly increased latency to first tumor. Here we used cDNA microarray analysis to elucidate the effects of the green tea polyphenol epigallocatechin-3 gallate (EGCG) on the gene expression profile in a DMBA-transformed breast cancer cell line. RNA was isolated, in quadruplicate, from D3-1 cells treated with 60 mug/mL EGCG for 2, 7, or 24 h and subjected to analysis. Semiquantitative RT-PCR and Northern blot analyses confirmed the changes in the expression of 12 representative genes seen in the microarray experiments. Overall, our results documented EGCG-altered expression of genes involved in nuclear and cytoplasmic transport, transformation, redox signaling, response to hypoxia, and PAHs.

9,10-Dimethyl-1,2-benzanthracene↗

Liquid chromatographic determination of St. John's wort components in functional foods.

A method was developed for determination of St. John's wort marker compounds hypericin, pseudohypericin, hyperforin, and adhyperforin in functional foods. Solid-phase extraction provided analyte extraction and significant sample cleanup prior to analysis using liquid chromatography (LC) with UV and fluorescence detection. In addition to quantification using LC-UV, confirmation was made with electrospray ionization LC mass spectrometry (LC/MS). Several commercially available tea and drink products claiming to contain St. John's wort were tested. Recoveries ranged from 51 to 98% for the liquid samples. Comparison of the concentrations in 4 St. John's wort teas showed a variation in analyte concentration (1044-10 ng/mL marker compounds in brewed tea) and composition. No marker compounds were found in the beverages, indicating possible decomposition of the marker compounds caused by low pH and/or exposure to light. A solvent extraction procedure was developed for analysis of the marker compounds from solid samples. Analytes were detected at low parts per million, with an average recovery of 75%. No St. John's wort components were found in the 2 solid functional food samples analyzed.

Anthracenes↗

Potential molecular targets of tea polyphenols in human tumor cells: significance in cancer prevention.

Next to water, tea is the most popular beverage in the world, and the cancer-preventive effects of this beverage have been suggested. Epidemiological studies have shown decreased cancer occurrence in those individuals who drink green tea regularly. A wealth of research suggests numerous mechanisms of action to explain these observations. The most abundant and popular compound studied in tea research is (-)-epigallocatechin-3-gallate (EGCG), which acts as a powerful antioxidant and can inhibit a number of tumor cell proliferation- and survival-related proteins. Tea polyphenols are known to inhibit the large multi-catalytic protease (the proteasome) and metaloproteionases, involved in tumor survival and metastasis, respectively. Additionally, tea polyphenols inhibit the activities of many tumor-associated protein kinases, including epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, mitogen-activated protein kinase, and IkB kinase. Tea polyphenols have also been found to inhibit some cancer-related proteins that regulate DNA replication and transformation. At present, it is not known which of these activities of tea polyphenols are required for its cancer-preventive effects. However, by understanding the in vivo concentrations of tea polyphenols required to inhibit each of these activities, we may start to sort out in the future the mechanisms responsible for the cancer-preventive effects of tea.

Animals↗

Brick tea consumption as the cause of dental fluorosis among children from Mongol, Kazak and Yugu populations in China.

Dietary fluoride intake and the prevalence of dental fluorosis were investigated in children from three population groups (mongol, Kazak and Yugu) in Gansu Province, China. The concentration of fluoride in drinking water ranged from 0.11 to 0.32 mg/litre; there was no other fluoride pollution. There was a high prevalence of dental fluorosis-52, 84 and 76% among the Mongol, Kazak and Yugu children, respectively). Dental fluorosis was particularly severe among the Kazak population (severity index: 2.00, 3.05 and 2.57 among the three populations, respectively). Each of the population groups had a long tradition of drinking milk tea made from brick tea water. This milk tea was found to contain high concentrations of fluoride (2.58-3.69 mg/litre). The daily fluorine consumption was 1.36-2.42-times the US RDA of 2.5 mg for children. Regression analysis showed that fluorosis was significantly correlated with the consumption of milk tea made from brick tea water, but not with any other dietary component (including milk).

Adolescent↗

Mechanistic findings of green tea as cancer preventive for humans.

Based on our initial work with green tea, in which repeated topical applications of (-)-epigallocatechin gallate (EGCG), the main green tea polyphenol, inhibited tumor promotion in a two-stage carcinogenesis experiment on mouse skin (Phytother Res 1, 44-47, 1987), numerous scientists have since provided so much additional evidence of the benefits of drinking green tea that it is now an acknowledged cancer preventive in Japan, and will possibly soon be recognized as such in other countries. Our work has so far produced several important results with EGCG and green tea: a wide range of target organs in animal experiments for cancer prevention, wide bioavailability of 3H-EGCG in various organs of mice, delayed cancer onset of patients with a history of consuming over 10 cups of green tea per day, and absence of any severe adverse effects among volunteers who took 15 green tea tablets per day (2.25 g green tea extracts, 337.5 mg EGCG, and 135 mg caffeine) for 6 months. This paper introduces three new findings: 1) EGCG interacted with the phospholipid bilayer membrane resulting in confirmation of the sealing effect of EGCG; 2) EGCG inhibited TNF-alpha gene expression in the cells and TNF-alpha release from the cells; 3) high consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal Stage I and II breast cancer patients, and with increased expression of progesterone and estrogen receptors among postmenopausal ones. These results provide new insights into our understanding of the mechanisms of action of tea polyphenols and green tea extract as a cancer preventive.

Antineoplastic Agents↗

Tea consumption and cancer.

Following the report from Hawaii (Heilbrun et al., 1986) of relationships between tea consumption and respectively rectal cancer (positive) and prostate cancer (negative), these questions were examined using data from a prospective mortality study of London men initiated in 1967. The small numbers of men who did not usually drink any tea prevented a reliable study of this sub group. Nevertheless no evidence of a dose-response relationship was found for rectal, colon or prostate cancer. Significant relationships were found, however, between tea consumption and deaths from stomach, lung and kidney cancers. In the case of stomach and lung cancer, these were partly due to the effects of social class and smoking, and possible reasons are considered for the residual relations.

Adult↗

Inhibition of benzo[a]pyrene-induced mutagenesis by (-)-epigallocatechin gallate in the lung of rpsL transgenic mice.

Epigallocatechin gallate (EGCG) is a major water-soluble component of green tea. The antimutagenic activity of EGCG against benzo[a]pyrene (B[a]P)-induced mutations was assessed by using transgenic mice carrying the rpsL gene as a monitor of mutations. Seven-week-old male mice were given drinking water containing EGCG for 3 weeks. On day 7, mice were treated with a single i.p. injection of B[a]P (500 mg/kg body wt). Two weeks after the injection, the mutations in the rpsL gene were analyzed. B[a]P treatment resulted in an approximately 4-fold increase of mutation frequency at the rpsL gene in the lung. An approximately 60% reduction in the B[a]P-induced mutations in the lung was observed when mice were given EGCG at concentrations >0.005%. B[a]P-induced mutations mainly occurred at G:C basepairs in the several specific nucleotide sequences of the rpsL gene. These were AGG, CGG, CGT, TGG, TGC and GGT: all of them contained a guanine residue. Mutations seen similarly in the human Ki-ras codon 12 or p53 codons 157, 248, and 273 of lung tumor were also found in the rpsL gene, and the mutations were suppressed by the EGCG treatment. In conclusion, the antimutagenic effects of EGCG for B[a]P-induced mutagenesis in vivo suggest that drinking green tea may reduce the tumor-initiating potency of B[a]P in the lung.

Animals↗

A case-control study of factors affecting the development of renal cell cancer.

A hospital-based case-control study was conducted between 1977 and 1983 of 189 men and 78 women with renal cell carcinoma at 18 hospital centers in six US cities and an equal number of controls matched on the basis of hospital, sex, race, age (+/- 5 years), and time of admission (+/- 12 months). Quetelet index (weight/height2) was found to be associated with renal cell cancer in both men and women. Crude odds ratios (ORs) for individuals in the upper tertile of the Quetelet index distribution (28 or more) were calculated to be 2.7 (95% confidence interval (CI) = 1.5-5.9) among men and 2.4 (95% CI = 1.2-6.8) among women compared to the lowest tertile. This relationship was found to be independent of the effects of cigarette smoking, chewing tobacco use, and decaffeinated coffee consumption. The use of chewing tobacco among men was positively associated with disease (OR = 4.0; 95% CI = 1.2-12.9). This was due primarily to a significant interaction between chewing tobacco use and cumulative cigarette smoking. The fitted odds ratio for persons who chewed tobacco and had 30 pack-years of cigarette smoke exposure, compared to never users of either tobacco product, was 26.0 (95% CI = 4.4-153.0) after adjusting for Quetelet index and decaffeinated coffee use. The odds ratio for decaffeinated coffee consumption among men and women combined was 1.9 (95% CI = 1.0-3.8) after controlling for other risk factors. A consistent dose-response was not found, however, by number of cups of decaffeinated coffee consumed per day. Those drinking 1-2 cups had an odds ratio of 2.0 while those drinking 3 cups or more per day had an odds ratio of 1.3, thus casting doubt on a causal interpretation of the finding. Alcohol drinkers had a lower, although not significantly different, rate of renal cell cancer than did never drinkers when the data were examined separately by sex. However, combining the data for both sexes yielded a crude odds ratio of 0.6 (95% CI = 0.4-1.0) for this association. There was no independent effect of tobacco smoking on the odds ratio for renal cell cancer. No significant differences between cases and controls were found for either the amount or duration of artificial sweetener use or the lifetime consumption of saccharin. Beverages such as caffeinated coffee, soft drinks, and tea, in addition to physical activity and occupation, were unrelated to the occurrence of disease.

Adult↗

A trial of oolong tea in the management of recalcitrant atopic dermatitis.

BACKGROUND: Mild cases of atopic dermatitis (AD) generally improve with standard treatment. However, standard treatment fails many patients with recalcitrant AD skin lesions. Study results in animal models have demonstrated that the administration of tea (ie, green, black, or oolong) has suppressed type I and type IV allergic reactions. OBJECTIVE: To test the effectiveness of oolong tea in the treatment of recalcitrant AD. PATIENTS: Although 121 patients with recalcitrant AD were enrolled in the study, 118 patients completed the open study. METHODS: Patients were asked to maintain their dermatological treatment. However, they were also instructed to drink oolong tea made from a 10-g teabag placed in 1000 mL of boiling water and steeped for 5 minutes. This amount was then divided into 3 equal servings and 1 serving was drunk daily after 3 regular meals. Photographs of 2 or 3 representative lesion sites were taken at baseline and at 1 and 6 months and the severity of pruritus was assessed on a 6-point Lickert-like scale ranging from markedly improved (>50% improvement) to worsened. RESULTS: After 1 month of treatment 74 (63%) of the 118 patients showed marked to moderate improvement of their condition. The beneficial effect was first noticed after 1 or 2 weeks of treatment. A good response to treatment was still observed in 64 patients (54%) at 6 months. CONCLUSION: The therapeutic efficacy of oolong tea in recalcitrant AD may well be the result of the antiallergic properties of tea polyphenols.

Adolescent↗

Green tea suppresses D-galactosamine-induced liver injury in rats.

Dietary supplementation with powder of a green tea extract suppressed the enhancement of plasma alanine aminotransferase and aspartate aminotransferase activities induced by D-galactosamine, but not by carbon tetrachloride, in a dose-dependent manner in rats. The minimum dose to cause a significant effect was 1 to 2%. Drinking green tea also suppressed plasma enzyme activities. These results indicate that green tea had a liver injury-preventive effect.

Alanine Transaminase↗

The effect of green tea on the activity of aldehyde dehydrogenase (ALDH) in the liver of rats during chronic ethanol consumption.

PURPOSE: Alterations in the redox state during chronic ethanol consumption are associated with the oxidation of ethanol via alcohol and aldehyde dehydrogenase. Among various antioxidants present in food, strong antioxidative effects have been attributed to polyphenols of green tea. The aim of the present study was to investigate the effect of green tea consumption during chronic ethanol intake on the activity of aldehyde dehydrogenase in the liver of rats during maturation and aging. MATERIALS AND METHODS: The activity of ALDH was measured in the livers of rats aged 2 (young), 12 (adult) and 24 months (old). The rats were fed with a control liquid Lieber DeCarli diet, control liquid diet containing green tea (3 g/l), ethanol liquid diet (with increasing ethanol dose from 2.3% to 7%) and ethanol liquid diet containing green tea. RESULTS: Chronic ethanol consumption significantly increased the liver ALDH activity in young and adult rats but decreased this activity in old animals. The drinking of green tea did not alter ALDH activity in ethanol-consuming rats. Drinking green tea alone significantly increased ALDH activity in young and adult rats but did not alter this activity in old rats. CONCLUSIONS: These results demonstrate that green tea administered during chronic ethanol consumption does not prevent the changes in the hepatic ALDH activity in the rats at each age.

Aldehyde Dehydrogenase↗

Black tea consumption and cancer risk: a prospective study.

In a prospective cohort study, men of Japanese ancestry were clinically examined from 1965 to 1968. For 7,833 of these men, data on black tea consumption habits were recorded. Since 1965, newly diagnosed cancer incidence cases have been identified: 152 colon, 151 lung, 149 prostate, 136 stomach, 76 rectum, 57 bladder, 30 pancreas, 25 liver, 12 kidney and 163 at other (miscellaneous) sites. Compared to almost-never drinkers, men habitually drinking black tea more than once/day had an increased relative risk (RR) for rectal cancer (RR = 4.2). This positive association (P = 0.0007) could not be accounted for by age or alcohol intake. We also observed a weaker but significant negative association of black tea intake and prostate cancer incidence (P = 0.020). There were no significant associations between black tea consumption and cancer at any other site.

Age Factors↗

Green tea consumption and serum malondialdehyde-modified LDL concentrations in healthy subjects.

OBJECTIVE: Green tea was shown to inhibit LDL oxidation, platelet aggregation, and matrix metalloproteinases (MMPs) activities in vitro. We tried to elucidate whether or not green tea consumption may have these effects in vivo, which may be protective against atherosclerotic disease. METHODS: We measured serum malondialdehyde-modified LDL (MDA-LDL) concentrations and urine 8-epi-prostaglandin (PG) F(2alpha) in 22 healthy male nonsmokers. They drank 7 cups/day of water for 2 weeks and drank 7 cups/day of green tea for the next 2 weeks. Regarding platelet aggregation, plasma thromboxane B(2) (TXB(2)) and 6-keto-PGF(1alpha) concentrations and ex vivo platelet aggregation were evaluated. Plasma MMP-2 and -9 concentrations were also measured. RESULTS: Of the 22 subjects, 20 had been in the habit of drinking green tea before the study. Plasma catechins concentrations significantly decreased at the end of the water period and then increased at the end of the green tea period. Although no change in plasma LDL-cholesterol concentrations (110 +/- 33 vs. 113 +/- 28 mg/dL, p = NS) was found, MDA-LDL concentrations (84 +/- 45 vs. 76 +/- 40 IU/L, p < 0.05) and the ratio of MDA-LDL/LDL-cholesterol (0.74 +/- 0.21 vs. 0.65 +/- 0.20, p < 0.02) significantly decreased at the end of the green tea period. However, no significant changes were observed in urine 8-epi-PGF(2alpha) concentrations, in platelet aggregation, nor in plasma TXB(2), 6-keto-PGF(1alpha) or MMP concentrations. CONCLUSION: Daily consumption of green tea decreased serum MDA-LDL concentrations, but it had no significant effects on platelet aggregation, platelet TX production or plasma MMPs concentrations. Our results suggest that green tea consumption may inhibit LDL oxidation in vivo.

Adult↗

Inhibition of 1,2-dimethylhydrazine-induced oxidative DNA damage by green tea extract in rat.

Following subcutaneous injection of 1,2-dimethylhydrazine (DMH), which is carcinogenic to rat colon and liver, to Sprague-Dawley rats, a significant increase of 8-hydroxydeoxyguanosine (8-OHdG) was observed in the DNA of colonic mucosa and liver. The 8-OHdG formation reached the maximal level at about 24 h after the DMII injection. On the other hand, no increase of 8-OHdG was observed in the DNA of the kidney. Drinking green tea extract (GTE) for ten days prior to the DMH injection significantly inhibited the formation of 8-OHdG in the colon. These findings demonstrate that DMH causes oxidative damage to the DNA of its target organ, and that GTE protects colonic mucosa from this oxidative damage.

1,2-Dimethylhydrazine↗

[Effects of tea on aberrant crypt foci and colorectal tumors in rats].

The present study was designed to investigate the chemopreventive effects of green tea and tea pigments (the main component of black tea) on 1,2-dimethylhydrazine (DMH)-induced rat colorectal carcinogenesis. Compared with the positive control group, green tea and tea pigments groups had less numbers of aberrant crypt foci (ACF) (P < 0.01) at the end of week 16. At the end of week 32, all rats in the positive control group developed colorectal tumors with an average of 2.6 tumors per rat, and a mean volume of 294.7 mm3 per tumor, while in the groups drinking green tea and tea pigments, the average numbers of colorectal tumors per rat were only 47.1% and 43.1% of controls respectively, and the mean tumor volume was inhibited by 77.1% and 68.1% respectively. It was concluded that tea pigments had a chemopreventive effect on colorectal tumor and ACF formation can be used as a useful intermediate end point to study chemopreventive effects on colorectal cancer.

1,2-Dimethylhydrazine↗

[The effect of Chinese teas on the occurrence of oesophageal tumor caused by N-nitrosomethylbenzylamine in rats].

Five groups of rats were given different varieties of Chinese tea as drinking water and on additional two groups of rats were given water with or without N-nitrosomethylbenzylamine (NMBzA) as controls. Except the control group, all the animals were intubated with NMBzA (5 mg.kg-1/wk) for 6 or 12 weeks. After 6 weeks, the incidence of oesophageal mucosa lesions was significantly lower in the tea-treated rats (16-59%) than the control group with NMBzA (100%). After 12 weeks, the incidence of oesophageal tumor was also significantly lower in the tea-treated groups (42-67%) than the control group with NMBzA (90%). Similar results were obtained in the tumor size and the number of tumors developed. The anti-carcinogenic effects of the 5 varieties of Chinese tea were also not the same the Fujian Oolong tea and Jasmine tea had the strongest effect. The results suggest that Chinese tea can inhibit the carcinogenesis caused by N-nitroso compound.

Animals↗

Tea catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans.

The effect of green tea catechin supplementation on antioxidant capacity of human plasma was investigated. Eighteen healthy male volunteers who orally ingested green tea extract (254 mg of total catechins/subject) showed 267 pmol of epigallocatechin-3-gallate (EGCg) per milliliter of plasma at 60 min after administration. The plasma phosphatidylcholine hydroperoxide (PCOOH) levels attenuated from 73.7 pmol/mL in the control to 44.6 pmol/mL in catechin-treated subjects, being correlated inversely with the increase in plasma EGCg level. The results suggested that drinking green tea contributes to prevent cardiovascular disease by increasing plasma antioxidant capacity in humans.

Adult↗

Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives.

The compound (-)-epigallocatechin-3-gallate (EGCG) is the major catechin found in green tea [Camellia sinensis L. Ktze. (Theaceae)]. This polyphenolic compound and several related catechins are believed to be responsible for the health benefits associated with the consumption of green tea. The potential health benefits ascribed to green tea and EGCG include antioxidant effects, cancer chemoprevention, improving cardiovascular health, enhancing weight loss, protecting the skin from the damage caused by ionizing radiation, and others. The compound EGCG has been shown to regulate dozens of disease-specific molecular targets. Many of these molecular targets are only affected by concentrations of EGCG that are far above the levels achieved by either drinking green tea or consuming moderate doses of green tea extract-based dietary supplements. In spite of this, well-designed double-blinded controlled clinical studies have recently demonstrated the efficacy of green tea extracts and purified EGCG products in patients. Therefore, this review highlights results from what the authors believe to be some of the most clinically significant recent studies and describes current developments in the stereoselective total synthesis of EGCG.

Animals↗