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Inhibition of Tumorigenesis

Tea and Cancer

Chung S. Yang, Zhi-Yuan Wang

Many laboratory studies have demonstrated the inhibitory effects of tea against Tumorigenesis in experimental animals.

SKIN. The inhibition of skin Tumorigenesis by tea and tea polyphenols has been observed by many investigators. Topical application of a green tea polyphenol fraction or its major component, EGCG, inhibited tumor initiation by 7,12-dimethylbenz (a) anthracene (DMBA) and benzo (a)pyrenediolepoxide (BPDE), as well as promotion byn 12-tetradecanoylphorbol-13-acetate (TPA), teleocidin, and okadaic acid in Sencar or CD-1 mice. Topical application of green tea polyphenols also inhibited tumor formation when 3-methylcholanthrene (3-MC) or ultraviolet light was used as the cancer-inducing agent. When given in drinking water, green tea infusions or polyphenols inhibited tumor initiation by DMBA, tumor promotion by TPA, and tumorigenesis by ultraviolet light in mice.

LUNG. Wu et al. Reported that oolong tea, jasmine tea, and green tea inhibited urethan-induced lung neoplasia in Kunming mice. In our laboratory, oral administration of green tea infusion (0.65% or 1.25%) as the sole source of drinking water to female A/J mice during the carcinogen-treatment period or postcarcinogen treatment period inhibited N-nitrosodiethylamine (NDEA)-induced lung tumorigenesis. Similar results were also observed with decaffeinated green tea or black tea extract (0.6%) against lung tumorigenesis induced by the tobacco carcinogen4- (methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK). When given during the carcinogen-treatment period, green tea and black tea extracts had the same effectiveness in inhibiting tumor multiplicity (by about 65%). When given after the carcinogen-treatment period, green tea appeared to be more effective than black tea. When 2% green tea infusion or EGCG was given to female A/J mice in drinking water during the NNK administration period (11.7 mg/kg by oral intubation once a week for 10 weeks), lung tumorigenesis was inhibited. It was also reported that oral feeding of 1.25% green tea infusion to A/J mice during the entire experimental period resulted in a statistically significant inhibition of BP or NDEA-induced lung tumorigenesis.

ESOPHAGUS. Oral administration of 2% tea infusions as the sole source of drinking water during the entire experimental period inhibited esophageal tumorigensis induced by N-nitrosomethylbenzylamine (NMBzA) in rats. In all, five brands of tea were tested and all were effective; the tumor incidence was reduced by 26%-53%, and tumor multiplicity was reduced by 58%-75%. Oral feeding of these tea infusions also markedly inhibited esophageal tumorigenesis caused by NMBzA precursors (methylbenzylamine plus sodium nitrite) in rats, reducing tumor incidence by 80%-90%. Oral feeding of green tea infusion also inhibited esophageal tumor formation induced by precursors of NMBzA or by nitrososarcosine in mice. In our laboratory, administration of 0.6% decaffeinated green tea or black tea extracts as the sole source of drinking water to Sprague-Dawley rats during the NMBzA-treatment period or after the NMBzA- treatment period decreased the papilloma multiplicity and reduced the size of esophageal papillomas. The dosage of NMBzA was 2.5 mg/kg injected subcutaneously twice weekly for 5 weeks.

FORESTOMACH. Oral administration of green tea infusion to female A/J mice during the carcinogen-treatment period, the post-NDEA-treatment period, or the entire experimental period inhibited NDEA-induced forestomach tumorigenesis. Oral feeding of green tea infusion also inhibited forestomach tumor formation induced by precursors of NMBzA or N-nitrososarcosine in mice. Recently, Wang et al. Reported that oral feeding of 1.2% green tea infusion to A/J mice during the entire experimental period resulted is a statistically significant inhibition of BP- or NDEA-induced forestomach tumorigenesis.

DUODENUM AND SMALL INTESTINE. Oral feeding of 0.005% EGCG (85% pure) in the drinking water after treatment of male C57BL/6 mice with N-ethyl-N’-nitro-N- nitrosoguanidine was reported to inhibit tumor formation in the duodenum. It is rather surprising that EGCG was effective at such a low dose. In a multigrain cancinogenesis model in which F344 rates were pretreated with combined administration of five carcinogens for the initial 4 weeks, Ito et al. demonstrated that 1% green tea polyphenols in the diet, given during or after the carcinogen exposure period, inhibited adenoma and adenocarcinoma formation in the small intestine. Dietary tea did not enhance tumor incidence in any organs evaluated.

COLON. One week after subcutaneous administration of azoxymethan to Fisher rats, oral feeding of 0.01% or 0.1% green tea polyphenols in drinking water for an additional 10 weeks resulted in the inhibition of colon carcinogenesis. However, in a multiorgan carcinogenesis model with rats, administration of 1% green tea polyphenols in the diet did not inhibit carcinogenesis in the colon.

LIVER. Chen et al. reported that administration of 5% green tea leaf in the diet from 10 days prior to an aflatoxinB1 treatment until 3 days after the treatment resulted in a statistically significant inhibition of aflatoxinB1-induced y-glutamyl transpeptidase-positive foci in the rat liver. It was also reported that 2.5% green tea leaf in the diet produced a statistically significant inhibition of NDEA-induced hepatocarcinogensis in rats. A solution of either 0.05% or 0.1% EGCG was effective in the inhibition of spontaneous hepatoma development in male C3H/HeN mice (Muto et al.: manuscript in preparation). Decaffeinated black tea extract given by oral gavage to male Swiss mice for 15 months also decreased tobacco-induced liver tumors.

PANCREAS. In a carcinogenesis model in which Syrian golden hamsters were treated with N-nitroso-bis(2-oxopropyl)amine and then put on a protein-deficient diet consisting of DL-ethionine and L-methionine for tumor promotion, dietary supplementation with green tea polyphenols (500mg/kg per day) during the promotion stage reduced pancreatic carcinogenesis.

MAMMARY GLAND. A preliminary experiment has shown that dietary intake of 1% green tea polyphenols did not have a statistically significant effect on the incidence of mammary tumors in female virgin SD rats pretreated with DMBA, but produced a statistically significant reduction of tumor size. When female C3H/HeN mice were fed with a complex of green tea polyphenols and aluminum hydroxide (0.2%) from birth to age 330 days, the spontaneous mammary tumor formation was markedly inhibited.

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