Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1997 Jun;105(Suppl 4):971–976. doi: 10.1289/ehp.97105s4971

Polyphenols as inhibitors of carcinogenesis.

C S Yang 1, M J Lee 1, L Chen 1, G Y Yang 1
PMCID: PMC1470038  PMID: 9255589

Abstract

Many polyphenolic compounds have demonstrated anticarcinogenic activities in animal models. These compounds include flavanone, flavonols, isoflavone, and catechins. In this article, tea catechins will be used as an example to illustrate current research in this area. Many laboratory studies have demonstrated the inhibition of tumorigenesis in animal models by different tea preparations. The animal models include tumorigenesis in the mouse lung, rat and mouse esophagi, mouse forestomach, mouse skin, mouse duodenum, rat small intestine, rat and mouse livers, and rat colon. In most of the studies, the inhibitory activity of tea could be demonstrated when tea preparations were given either during or after the carcinogen treatment period. Black tea was also effective, although the activity was weaker than green tea in some experiments. Decaffeinated tea preparations were also active in many model systems. The molecular mechanisms for these broad inhibitory actions are not fully understood. They are most likely related to the biochemical actions of the tea polyphenols, which include antioxidative activities and inhibition of cell proliferation and of tumor promotion-related activities. The effect of tea consumption on human cancers is not clear in spite of numerous investigations. The bioavailability and pharmacokinetics of tea polyphenols are being studied in animals and humans to provide a basis for more quantitative analyses on the effect of tea on carcinogenesis. More mechanistic and dose-response studies will help us to understand the effects of tea consumption on human carcinogenesis.

Full text

PDF
971

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames B. N., Gold L. S., Willett W. C. The causes and prevention of cancer. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5258–5265. doi: 10.1073/pnas.92.12.5258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bailey D. G., Arnold J. M., Spence J. D. Grapefruit juice and drugs. How significant is the interaction? Clin Pharmacokinet. 1994 Feb;26(2):91–98. doi: 10.2165/00003088-199426020-00002. [DOI] [PubMed] [Google Scholar]
  3. Barnes S., Peterson T. G., Coward L. Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. J Cell Biochem Suppl. 1995;22:181–187. doi: 10.1002/jcb.240590823. [DOI] [PubMed] [Google Scholar]
  4. Baron J. A., Gerhardsson de Verdier M., Ekbom A. Coffee, tea, tobacco, and cancer of the large bowel. Cancer Epidemiol Biomarkers Prev. 1994 Oct-Nov;3(7):565–570. [PubMed] [Google Scholar]
  5. Blot W. J., Li J. Y., Taylor P. R., Guo W., Dawsey S., Wang G. Q., Yang C. S., Zheng S. F., Gail M., Li G. Y. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst. 1993 Sep 15;85(18):1483–1492. doi: 10.1093/jnci/85.18.1483. [DOI] [PubMed] [Google Scholar]
  6. Bu-Abbas A., Clifford M. N., Walker R., Ioannides C. Selective induction of rat hepatic CYP1 and CYP4 proteins and of peroxisomal proliferation by green tea. Carcinogenesis. 1994 Nov;15(11):2575–2579. doi: 10.1093/carcin/15.11.2575. [DOI] [PubMed] [Google Scholar]
  7. Buening M. K., Chang R. L., Huang M. T., Fortner J. G., Wood A. W., Conney A. H. Activation and inhibition of benzo(a)pyrene and aflatoxin B1 metabolism in human liver microsomes by naturally occurring flavonoids. Cancer Res. 1981 Jan;41(1):67–72. [PubMed] [Google Scholar]
  8. Cerutti P. A. Mechanisms of action of oxidant carcinogens. Cancer Detect Prev. 1989;14(2):281–284. [PubMed] [Google Scholar]
  9. Chen J. The effects of Chinese tea on the occurrence of esophageal tumors induced by N-nitrosomethylbenzylamine in rats. Prev Med. 1992 May;21(3):385–391. doi: 10.1016/0091-7435(92)90046-k. [DOI] [PubMed] [Google Scholar]
  10. Cheng S., Ding L., Zhen Y., Lin P., Zhu Y., Chen Y., Hu X. Progress in studies on the antimutagenicity and anticarcinogenicity of green tea epicatechins. Chin Med Sci J. 1991 Dec;6(4):233–238. [PubMed] [Google Scholar]
  11. Dhar G. M., Shah G. N., Naheed B., Hafiza Epidemiological trend in the distribution of cancer in Kashmir Valley. J Epidemiol Community Health. 1993 Aug;47(4):290–292. doi: 10.1136/jech.47.4.290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ewertz M. Breast cancer in Denmark. Incidence, risk factors, and characteristics of survival. Acta Oncol. 1993;32(6):595–615. doi: 10.3109/02841869309092438. [DOI] [PubMed] [Google Scholar]
  13. Feig D. I., Reid T. M., Loeb L. A. Reactive oxygen species in tumorigenesis. Cancer Res. 1994 Apr 1;54(7 Suppl):1890s–1894s. [PubMed] [Google Scholar]
  14. Gao Y. T., McLaughlin J. K., Blot W. J., Ji B. T., Dai Q., Fraumeni J. F., Jr Reduced risk of esophageal cancer associated with green tea consumption. J Natl Cancer Inst. 1994 Jun 1;86(11):855–858. doi: 10.1093/jnci/86.11.855. [DOI] [PubMed] [Google Scholar]
  15. Graham H. N. Green tea composition, consumption, and polyphenol chemistry. Prev Med. 1992 May;21(3):334–350. doi: 10.1016/0091-7435(92)90041-f. [DOI] [PubMed] [Google Scholar]
  16. Gryglewski R. J., Korbut R., Robak J., Swies J. On the mechanism of antithrombotic action of flavonoids. Biochem Pharmacol. 1987 Feb 1;36(3):317–322. doi: 10.1016/0006-2952(87)90288-7. [DOI] [PubMed] [Google Scholar]
  17. Guengerich F. P., Kim D. H. In vitro inhibition of dihydropyridine oxidation and aflatoxin B1 activation in human liver microsomes by naringenin and other flavonoids. Carcinogenesis. 1990 Dec;11(12):2275–2279. doi: 10.1093/carcin/11.12.2275. [DOI] [PubMed] [Google Scholar]
  18. Han C., Xu Y. The effect of Chinese tea on occurrence of esophageal tumor induced by N-nitrosomethylbenzylamine in rats. Biomed Environ Sci. 1990 Mar;3(1):35–42. [PubMed] [Google Scholar]
  19. Hansson L. E., Nyrén O., Bergström R., Wolk A., Lindgren A., Baron J., Adami H. O. Diet and risk of gastric cancer. A population-based case-control study in Sweden. Int J Cancer. 1993 Sep 9;55(2):181–189. doi: 10.1002/ijc.2910550203. [DOI] [PubMed] [Google Scholar]
  20. Hu J., Nyrén O., Wolk A., Bergström R., Yuen J., Adami H. O., Guo L., Li H., Huang G., Xu X. Risk factors for oesophageal cancer in northeast China. Int J Cancer. 1994 Apr 1;57(1):38–46. doi: 10.1002/ijc.2910570108. [DOI] [PubMed] [Google Scholar]
  21. Huang C., Zhang X., Qiao Z., Guan L., Peng S., Liu J., Xie R., Zheng L. A case-control study of dietary factors in patients with lung cancer. Biomed Environ Sci. 1992 Sep;5(3):257–265. [PubMed] [Google Scholar]
  22. Huang M. T., Ho C. T., Wang Z. Y., Ferraro T., Finnegan-Olive T., Lou Y. R., Mitchell J. M., Laskin J. D., Newmark H., Yang C. S. Inhibitory effect of topical application of a green tea polyphenol fraction on tumor initiation and promotion in mouse skin. Carcinogenesis. 1992 Jun;13(6):947–954. doi: 10.1093/carcin/13.6.947. [DOI] [PubMed] [Google Scholar]
  23. Katiyar S. K., Agarwal R., Wood G. S., Mukhtar H. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-caused tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated SENCAR mouse skin by a polyphenolic fraction isolated from green tea. Cancer Res. 1992 Dec 15;52(24):6890–6897. [PubMed] [Google Scholar]
  24. Khan S. G., Katiyar S. K., Agarwal R., Mukhtar H. Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention. Cancer Res. 1992 Jul 15;52(14):4050–4052. [PubMed] [Google Scholar]
  25. Kinlen L. J., McPherson K. Pancreas cancer and coffee and tea consumption: a case-control study. Br J Cancer. 1984 Jan;49(1):93–96. doi: 10.1038/bjc.1984.14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kono S., Ikeda M., Tokudome S., Kuratsune M. A case-control study of gastric cancer and diet in northern Kyushu, Japan. Jpn J Cancer Res. 1988 Oct;79(10):1067–1074. doi: 10.1111/j.1349-7006.1988.tb01528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lee M. J., Wang Z. Y., Li H., Chen L., Sun Y., Gobbo S., Balentine D. A., Yang C. S. Analysis of plasma and urinary tea polyphenols in human subjects. Cancer Epidemiol Biomarkers Prev. 1995 Jun;4(4):393–399. [PubMed] [Google Scholar]
  28. Mashberg A., Boffetta P., Winkelman R., Garfinkel L. Tobacco smoking, alcohol drinking, and cancer of the oral cavity and oropharynx among U.S. veterans. Cancer. 1993 Aug 15;72(4):1369–1375. doi: 10.1002/1097-0142(19930815)72:4<1369::aid-cncr2820720436>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  29. Mellemgaard A., Engholm G., McLaughlin J. K., Olsen J. H. Risk factors for renal cell carcinoma in Denmark. I. Role of socioeconomic status, tobacco use, beverages, and family history. Cancer Causes Control. 1994 Mar;5(2):105–113. doi: 10.1007/BF01830256. [DOI] [PubMed] [Google Scholar]
  30. Memik F., Nak S. G., Gulten M., Ozturk M. Gastric carcinoma in northwestern Turkey: epidemiologic characteristics. J Environ Pathol Toxicol Oncol. 1992 Sep-Oct;11(5-6):335–338. [PubMed] [Google Scholar]
  31. Mizuno S., Watanabe S., Nakamura K., Omata M., Oguchi H., Ohashi K., Ohyanagi H., Fujiki T., Motojima K. A multi-institute case-control study on the risk factors of developing pancreatic cancer. Jpn J Clin Oncol. 1992 Aug;22(4):286–291. [PubMed] [Google Scholar]
  32. Narisawa T., Fukaura Y. A very low dose of green tea polyphenols in drinking water prevents N-methyl-N-nitrosourea-induced colon carcinogenesis in F344 rats. Jpn J Cancer Res. 1993 Oct;84(10):1007–1009. doi: 10.1111/j.1349-7006.1993.tb02792.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Obermeier M. T., White R. E., Yang C. S. Effects of bioflavonoids on hepatic P450 activities. Xenobiotica. 1995 Jun;25(6):575–584. doi: 10.3109/00498259509061876. [DOI] [PubMed] [Google Scholar]
  34. Olsen J., Kronborg O. Coffee, tobacco and alcohol as risk factors for cancer and adenoma of the large intestine. Int J Epidemiol. 1993 Jun;22(3):398–402. doi: 10.1093/ije/22.3.398. [DOI] [PubMed] [Google Scholar]
  35. Pavlidis N. A., Briassoulis E., Klouvas G., Bai M. Is interferon-a an active agent in Castleman's disease? Ann Oncol. 1992 Jan;3(1):85–86. doi: 10.1093/oxfordjournals.annonc.a058082. [DOI] [PubMed] [Google Scholar]
  36. Shi S. T., Wang Z. Y., Smith T. J., Hong J. Y., Chen W. F., Ho C. T., Yang C. S. Effects of green tea and black tea on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone bioactivation, DNA methylation, and lung tumorigenesis in A/J mice. Cancer Res. 1994 Sep 1;54(17):4641–4647. [PubMed] [Google Scholar]
  37. Shibata A., Mack T. M., Paganini-Hill A., Ross R. K., Henderson B. E. A prospective study of pancreatic cancer in the elderly. Int J Cancer. 1994 Jul 1;58(1):46–49. doi: 10.1002/ijc.2910580109. [DOI] [PubMed] [Google Scholar]
  38. Shiraki M., Hara Y., Osawa T., Kumon H., Nakayama T., Kawakishi S. Antioxidative and antimutagenic effects of theaflavins from black tea. Mutat Res. 1994 Jan-Feb;323(1-2):29–34. doi: 10.1016/0165-7992(94)90041-8. [DOI] [PubMed] [Google Scholar]
  39. Slattery M. L., West D. W. Smoking, alcohol, coffee, tea, caffeine, and theobromine: risk of prostate cancer in Utah (United States). Cancer Causes Control. 1993 Nov;4(6):559–563. doi: 10.1007/BF00052432. [DOI] [PubMed] [Google Scholar]
  40. Sohn O. S., Surace A., Fiala E. S., Richie J. P., Jr, Colosimo S., Zang E., Weisburger J. H. Effects of green and black tea on hepatic xenobiotic metabolizing systems in the male F344 rat. Xenobiotica. 1994 Feb;24(2):119–127. doi: 10.3109/00498259409043226. [DOI] [PubMed] [Google Scholar]
  41. Stich H. F. Teas and tea components as inhibitors of carcinogen formation in model systems and man. Prev Med. 1992 May;21(3):377–384. doi: 10.1016/0091-7435(92)90045-j. [DOI] [PubMed] [Google Scholar]
  42. Stocks P. Cancer mortality in relation to national consumption of cigarettes, solid fuel, tea and coffee. Br J Cancer. 1970 Jun;24(2):215–225. doi: 10.1038/bjc.1970.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Trela B. A., Carlson G. P. Effect of flavanone on mixed-function oxidase and conjugation reactions in rats. Xenobiotica. 1987 Jan;17(1):11–16. doi: 10.3109/00498258709047170. [DOI] [PubMed] [Google Scholar]
  44. Wakai K., Ohno Y., Obata K., Aoki K. Prognostic significance of selected lifestyle factors in urinary bladder cancer. Jpn J Cancer Res. 1993 Dec;84(12):1223–1229. doi: 10.1111/j.1349-7006.1993.tb02826.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wang Z. Y., Agarwal R., Bickers D. R., Mukhtar H. Protection against ultraviolet B radiation-induced photocarcinogenesis in hairless mice by green tea polyphenols. Carcinogenesis. 1991 Aug;12(8):1527–1530. doi: 10.1093/carcin/12.8.1527. [DOI] [PubMed] [Google Scholar]
  46. Wang Z. Y., Agarwal R., Khan W. A., Mukhtar H. Protection against benzo[a]pyrene- and N-nitrosodiethylamine-induced lung and forestomach tumorigenesis in A/J mice by water extracts of green tea and licorice. Carcinogenesis. 1992 Aug;13(8):1491–1494. doi: 10.1093/carcin/13.8.1491. [DOI] [PubMed] [Google Scholar]
  47. Wang Z. Y., Hong J. Y., Huang M. T., Reuhl K. R., Conney A. H., Yang C. S. Inhibition of N-nitrosodiethylamine- and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced tumorigenesis in A/J mice by green tea and black tea. Cancer Res. 1992 Apr 1;52(7):1943–1947. [PubMed] [Google Scholar]
  48. Wang Z. Y., Huang M. T., Ferraro T., Wong C. Q., Lou Y. R., Reuhl K., Iatropoulos M., Yang C. S., Conney A. H. Inhibitory effect of green tea in the drinking water on tumorigenesis by ultraviolet light and 12-O-tetradecanoylphorbol-13-acetate in the skin of SKH-1 mice. Cancer Res. 1992 Mar 1;52(5):1162–1170. [PubMed] [Google Scholar]
  49. Wang Z. Y., Huang M. T., Ho C. T., Chang R., Ma W., Ferraro T., Reuhl K. R., Yang C. S., Conney A. H. Inhibitory effect of green tea on the growth of established skin papillomas in mice. Cancer Res. 1992 Dec 1;52(23):6657–6665. [PubMed] [Google Scholar]
  50. Wang Z. Y., Khan W. A., Bickers D. R., Mukhtar H. Protection against polycyclic aromatic hydrocarbon-induced skin tumor initiation in mice by green tea polyphenols. Carcinogenesis. 1989 Feb;10(2):411–415. doi: 10.1093/carcin/10.2.411. [DOI] [PubMed] [Google Scholar]
  51. Wang Z. Y., Wang L. D., Lee M. J., Ho C. T., Huang M. T., Conney A. H., Yang C. S. Inhibition of N-nitrosomethylbenzylamine-induced esophageal tumorigenesis in rats by green and black tea. Carcinogenesis. 1995 Sep;16(9):2143–2148. doi: 10.1093/carcin/16.9.2143. [DOI] [PubMed] [Google Scholar]
  52. Xu Y., Ho C. T., Amin S. G., Han C., Chung F. L. Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis in A/J mice by green tea and its major polyphenol as antioxidants. Cancer Res. 1992 Jul 15;52(14):3875–3879. [PubMed] [Google Scholar]
  53. Yamane T., Hagiwara N., Tateishi M., Akachi S., Kim M., Okuzumi J., Kitao Y., Inagake M., Kuwata K., Takahashi T. Inhibition of azoxymethane-induced colon carcinogenesis in rat by green tea polyphenol fraction. Jpn J Cancer Res. 1991 Dec;82(12):1336–1339. doi: 10.1111/j.1349-7006.1991.tb01801.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Yamane T., Takahashi T., Kuwata K., Oya K., Inagake M., Kitao Y., Suganuma M., Fujiki H. Inhibition of N-methyl-N'-nitro-N-nitrosoguanidine-induced carcinogenesis by (-)-epigallocatechin gallate in the rat glandular stomach. Cancer Res. 1995 May 15;55(10):2081–2084. [PubMed] [Google Scholar]
  55. Yan Y. S. [The experiment of tumor-inhibiting effect of green tea extract in animal and human body]. Zhonghua Yu Fang Yi Xue Za Zhi. 1993 May;27(3):129–131. [PubMed] [Google Scholar]
  56. Yang C. S., Sun Y., Yang Q. U., Miller K. W., Li G. Y., Zheng S. F., Ershow A. G., Blot W. J., Li J. Y. Vitamin A and other deficiencies in Linxian, a high esophageal cancer incidence area in northern China. J Natl Cancer Inst. 1984 Dec;73(6):1449–1453. [PubMed] [Google Scholar]
  57. Yang C. S., Wang Z. Y. Tea and cancer. J Natl Cancer Inst. 1993 Jul 7;85(13):1038–1049. doi: 10.1093/jnci/85.13.1038. [DOI] [PubMed] [Google Scholar]
  58. Yu G. P., Hsieh C. C. Risk factors for stomach cancer: a population-based case-control study in Shanghai. Cancer Causes Control. 1991 May;2(3):169–174. doi: 10.1007/BF00056210. [DOI] [PubMed] [Google Scholar]
  59. Zatonski W. A., Boyle P., Przewozniak K., Maisonneuve P., Drosik K., Walker A. M. Cigarette smoking, alcohol, tea and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland. Int J Cancer. 1993 Feb 20;53(4):601–607. doi: 10.1002/ijc.2910530413. [DOI] [PubMed] [Google Scholar]
  60. Zheng S. F., Ershow A. G., Yang C. S., Li G. Y., Li R. S., Li H., Zou X. L., Liu X. F., Song L. H., Qing Q. S. Nutritional status in Linxian, China: effects of season and supplementation. Int J Vitam Nutr Res. 1989;59(2):190–199. [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES