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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Mechanistic findings of green tea as cancer preventive for humans. 1020 93

A growing body of evidence from studies in laboratory animals indicates that green tea protects against cancer development at various organ sites. We have previously shown that green tea, administered as drinking water, inhibits lung tumor development in A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-l-butanone (NNK), a potent nicotine-derived lung carcinogen found in tobacco. The inhibitory effect of green tea has been attributed to its major polyphenolic compound, epigallocatechin gallate (EGCG), and, to a lesser extent, to caffeine. We have also demonstrated that while levels of O6-methylguanine, a critical lesion in NNK lung tumorigenesis, were not affected in lung DNA. However, the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage, were significantly suppressed in mice treated with green tea or EGCG. These studies underscore the importance of the antioxidant activity of green tea and EGCG for their inhibitory activity against lung tumorigenesis. Unlike green tea, the effect of black tea on carcinogenesis has been scarcely studied, even though the worldwide production and consumption of black tea far exceeds that of green tea. The oxidation products found in black tea, thearubigins and theaflavins, also possess antioxidant activity, suggesting that black tea may also inhibit NNK-induced lung tumorigenesis. Indeed, bioassays in A/J mice have shown that black tea given as drinking water retarded the development of lung cancer caused by NNK. However, data on the relationship of black tea consumption with the lung cancer risk in humans are limited and inconclusive. There is a need for additional tumor bioassays in animal models to better examine the protective role of black tea against lung cancer. The development of adenocarcinomas and adenosquamous carcinomas in F344 rats upon chronic administration of NNK provides an important and relevant model for lung carcinogenesis in smokers. Thus far, no information was previously available regarding the effects of tea on this model. We conducted a 2-year lifetime bioassay in F344 rats to determine whether black tea and caffeine are protective against lung tumorigenesis induced by NNK. Our studies in both mice and rats have generated important new data that support green and black tea and caffeine as potential preventive agents against lung cancer, suggesting that a closer examination of the roles of tea and caffeine on lung cancer in smokers may be warranted.
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PMID:The prevention of lung cancer induced by a tobacco-specific carcinogen in rodents by green and black Tea. 1020 97

Modifying effects of caffeine, alpha-tocopherol, and n-tritriacontane-16,18-dione (TTAD) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary and colonic carcinogenesis were investigated in female F344 rats. Groups of 20 rats, 6 weeks old, were given 0.02% PhIP (in diet) alone, or together with 0.1% caffeine (in drinking water), 0.5% alpha-tocopherol (in diet) or 0.1% TTAD (in diet) for up to 54 weeks. Groups of 10 females receiving basal diet or one of the test chemicals without PhIP supplementation were also maintained. The final combined incidences (adenomas plus adenocarcinomas) and multiplicity (No./rat) of mammary adenomas and adenocarcinomas were significantly lowered in the PhIP plus caffeine group (10%, 0.10) as compared to the PhIP alone value (40%, (1.50). Incidences of mammary tumors in the PhIP plus alpha-tocopherol or TTAD groups tended to be decreased while their multiplicities were significantly lowered. With regard to colon tumor development, on the other hand, rats given PhIP plus caffeine exhibited an elevated incidence (75% versus 15% in the control), whereas alpha-tocopherol and TTAD had no effect. Surprisingly, metabolic activation of PhIP was inhibited by addition of caffeine in an in vitro assay. The results indicate that caffeine exerts a potent chemopreventive action against PhIP-induced mammary carcinogenesis, but acts as a co-carcinogen for PhIP-induced colonic carcinogenesis.
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PMID:Organ-dependent modifying effects of caffeine, and two naturally occurring antioxidants alpha-tocopherol and n-tritriacontane-16,18-dione, on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary and colonic carcinogenesis in female F344 rats. 1036 77

Treatment of SKH-1 mice with ultraviolet B light (UV-B, 30 mJ/cm2) twice a week for 22-23 weeks resulted in tumor-free animals with a high risk of developing malignant and nonmalignant tumors during the next several months in the absence of further UV-B treatment (high-risk mice). In three separate experiments, oral administration of green tea or black tea (4-6 mg tea solids/ml) as the sole source of drinking fluid for 18-23 weeks to these high-risk mice inhibited the formation and decreased the size of nonmalignant squamous cell papillomas and keratoacanthomas as well as the formation and size of malignant squamous cell carcinomas. In one experiment all these inhibitory effects of tea were statistically significant, whereas in the two other experiments many but not all of the inhibitory effects of tea were statistically significant. The decaffeinated teas were inactive or less effective inhibitors of tumor formation than the regular teas, and adding caffeine back to the decaffeinated teas restored biological activity. Oral administration of caffeine alone (0.44 mg/ml) as the sole source of drinking fluid for 18-23 weeks inhibited the formation of nonmalignant and malignant tumors, and this treatment also decreased tumor size in these high-risk mice.
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PMID:Effects of oral administration of tea, decaffeinated tea, and caffeine on the formation and growth of tumors in high-risk SKH-1 mice previously treated with ultraviolet B light. 1036 9

The purpose of this study was to evaluate hepatic metabolic capacity in cirrhotic patients with hepatocellular carcinoma (HCC). We compared plasma caffeine clearance, calculated by two point analysis, between patients with cirrhosis alone and cirrhosis complicated with HCC. These two groups were comparable with regards to age, sex, and the severity of liver disease, graded by Child-Pugh score as compensated and decompensated cases. From our result, caffeine clearance in compensated cases was clearly higher than that of decompensated cases in both groups studied, particularly in the HCC group (p = 0.001). The mean value of caffeine clearance in HCC patients correlated well with the tumor staging as classified by Okuda's criteria. There was also a reversal correlation between tumor size and the clearance tested in compensated cases of HCC (p = 0.046), but this finding was not detected in decompensated cases (p > 0.05). We conclude that the determination of caffeine clearance can serve as a useful parameter for the assessment of hepatic functional reserve in cirrhotic patients complicated with HCC, and may be a useful predictor for survival outcome.
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PMID:Caffeine clearance study in hepatocellular carcinoma. 1041 Apr 86

Caffeine exposure sensitizes tumor cells to ionizing radiation and other genotoxic agents. The radiosensitizing effects of caffeine are associated with the disruption of multiple DNA damage-responsive cell cycle checkpoints. The similarity of these checkpoint defects to those seen in ataxia-telangiectasia (A-T) suggested that caffeine might inhibit one or more components in an A-T mutated (ATM)-dependent checkpoint pathway in DNA-damaged cells. We now show that caffeine inhibits the catalytic activity of both ATM and the related kinase, ATM and Rad3-related (ATR), at drug concentrations similar to those that induce radiosensitization. Moreover, like ATM-deficient cells, caffeine-treated A549 lung carcinoma cells irradiated in G2 fail to arrest progression into mitosis, and S-phase-irradiated cells exhibit radioresistant DNA synthesis. Similar concentrations of caffeine also inhibit gamma- and UV radiation-induced phosphorylation of p53 on Ser15, a modification that may be directly mediated by the ATM and ATR kinases. DNA-dependent protein kinase, another ATM-related protein involved in DNA damage repair, was resistant to the inhibitory effects of caffeine. Likewise, the catalytic activity of the G2 checkpoint kinase, hChk1, was only marginally suppressed by caffeine but was inhibited potently by the structurally distinct radiosensitizer, UCN-01. These data suggest that the radiosensitizing effects of caffeine are related to inhibition of the protein kinase activities of ATM and ATR and that both proteins are relevant targets for the development of novel anticancer agents.
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PMID:Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. 1048 86

The bacterial cytolethal distending toxin (CDT) was previously shown to arrest the tumor-derived HeLa cell line in the G2-phase of the cell cycle through inactivation of CDK1, a cyclin-dependent kinase whose state of activation determines entry into mitosis. We have analysed the effects induced in HeLa cells by CDT, in comparison to those induced by etoposide, a prototype anti-tumoral agent that triggers a G2 cell cycle checkpoint by inducing DNA damage. Both CDT and etoposide inhibit cell proliferation and induces the formation of enlarged mononucleated cells blocked in G2. In both cases, CDK1 from arrested cells could be reactivated both in vitro by dephosphorylation by recombinant Cdc25B phosphatase and in vivo by caffeine. However, the cell cycle arrest triggered by CDT, unlike etoposide, did not originate from DNA strand breaks as demonstrated in the single cell gel electrophoresis assay and by the absence of slowing down of S phase in synchronized cells. Together with additional observations on synchronized HeLa cells, our results suggest that CDT triggers a G2 cell cycle checkpoint that is initiated during DNA replication and that is independent of DNA damage.
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PMID:The bacterial cytolethal distending toxin (CDT) triggers a G2 cell cycle checkpoint in mammalian cells without preliminary induction of DNA strand breaks. 1059 28

In Asia, nontoxic dietary products are considered desirable primary prevention vehicles for conquering cancer. As early as 1978, investigators in Korea carried out extensive long-term anticarcinogenicity experiments using the mouse lung tumor model and observed an anticarcinogenic effect of Panax ginseng C.A. Meyer extract in 1980. The results showed that natural products can provide hope for human cancer prevention. A newly established nine-week medium-term model using mouse lung tumors (Yun's model) could confirm the anticarcinogenicity of ginseng that varies according to its type and age. Subsequently, the ginseng was shown by epidemiological studies to be a nonorgan-specific cancer preventive agent associated with a dose-response relationship. The anticarcinogenic effects of vegetarian foods common at every dining table in Korea and some synthetics were also studied using Yun's nine-week model. In brief, ascorbic acid, soybean lecithin, capsaicin, biochanin A, Ganoderma lucidum, caffeine, and a novel synthetic 2-(allylthio)pyrazine decrease the incidence of mouse lung tumors, whereas fresh ginseng (4 years old), carrot, spinach, Sesamum indicum, beta-carotene, and 13-cis retinoic acid do not. This result regarding beta-carotene is consistent with the ineffective findings of the ATBC trial, the CARET trial, and the Physicians' Health Study. In 1983, a cancer chemoprevention study group was first established in Japan. Subsequently, (-)-epigallocatechin gallate, cryptoporic acid E, and sarcophytol A from natural products, and synthetic acyclic retinoid and canventol were shown to be anticarcinogenic or chemopreventive in human subjects. Despite the frequent consumption of tea wordwide as a beverage and current experimental evidence of anticarcinogenesis, including controversial results of epidemiological studies, more systematic clinical trials for confirmation of preventive activity of tea against cancer are needed. Placebo-controlled intervention trials of dietary fiber are under study in Japan. In the past decade, new triterpenoids were isolated from various natural sources, and its biological activities were investigated in Asia. In the late 1970s a comprehensive chemoprevention program was established at the Institute of Materia Medica, Chinese Academy of Medical Sciences. Since then, many retinoid compounds have been synthesized and screened in the search for chemopreventive cancer agents. The National Cancer Institute (USA) and China are jointly engaged in the two-nutrition intervention in Linxian, China. The results of joint study of the general population and of dysplasia in China should stimulate further research to clarify the potential benefits of micronutrient supplements. We need to clarify if there is a connection between the lower rates of cancer mortality in Korea and the frequent consumption of anticarcinogenic vegetables or traditional foods, including ginseng and Ganoderma lucidum. The constituents of the nontoxic stable dietary products promise to be the future hope for conquering cancers in the coming years.
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PMID:Update from Asia. Asian studies on cancer chemoprevention. 1066 93

The radiosensitizing effects of caffeine on two rat yolk sac tumor cell lines with a different p53 status were investigated. A reduction of radiation-induced G(2) arrest was caused by caffeine at a concentration of 2 mM in both cell lines. The reduction of survival was observed in a combination of radiation and 2 mM caffeine only in a lower radiation dose range, but not in a higher dose range in NMT-1 with a wild type p53. Radiosensitization of caffeine was recognized even in a higher dose range for cells with a mutant-type p53. Apoptosis, which was not prominent after irradiation alone or caffeine treatment alone, was induced by irradiation in combination with caffeine in cells with a mutant-type p53 through a p53-independent pathway.
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PMID:Caffeine enhanced radiosensitivity of rat tumor cells with a mutant-type p53 by inducing apoptosis in a p53-independent manner. 1077 7

Tea is one of the most widely consumed beverages, second only to water. Many experimental researches in laboratory animals demonstrated that tea components had an inhibitory effect on carcinogenesis at a number of organ sites. The inhibitory effects of tea against carcinogenesis have been attributed to the biologic activities of the polyphenol fraction in tea. This review summarizes experimental data on chemopreventive effects of tea polyphenols in various tumor bioassay systems. Many laboratory studies have demonstrated the inhibitory effects of green tea polyphenols, especially (-)-epigallocatechin-3-gallate (EGCG), on carcinogenesis in animals models. The majority of these studies have been conducted in mouse skin tumor models, where tea polyphenols were used either as oral feeding in drinking water or in direct local application. Most studies used 12-O-tetradecanoylphorbol-13-acetate (TPA) or ultraviolet (UV) radiation as the tumor promoter and found anticarcinogenic effects caused by green tea polyphenols. Black tea was also found to be effective, although the activity was weaker than that of green tea in some experiments. Other studies showed that black tea polyphenols-theaflavins exhibited stronger anticarcinogenic activity than did EGCG. Caffeine in tea was also important for tea to prevent tumorigenesis. The molecular mechanisms of the cancer chemopreventive effects of tea polyphenols are not completely understood. They are most likely related to the mechanisms of biochemical actions of tea polyphenols, which include antioxidative activities, modulation of xenobiotic metabolite enzymes and inhibition of tumor promotion. In addition, we have also proposed that tea polyphenols function as cancer chemopreventive agents through modulation of mitotic signal transduction. However, the molecular mechanisms involved in this modulation need further investigation.
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PMID:Cancer chemoprevention by tea polyphenols. 1078 33


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