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Challenging the effectiveness of green tea in primary and tertiary cancer prevention

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Abstract

Purpose

Drinking green tea daily is part of Japanese culture, and various studies have revealed that green tea is a cancer preventive. We here review our progress in cancer prevention with green tea on 12 main topics, from basic to clinical level.

Topics and methods

Biochemical and biological studies of green tea catechins, a prospective cohort study, preclinical safety trials with tablets of green tea extract, double-blind randomized clinical phase II prevention trial for recurrence of colorectal adenomas, and synergistically enhanced inhibition by the combination of green tea catechins and anticancer drugs. All results were significant, including human studies with informed consent.

Results

Drinking 10 Japanese-size cups of green tea per day delayed the cancer onset of humans 7 years for females. For tertiary cancer prevention, consuming 10 cups of green tea per day fortified by green tea tablets, 50 %, significantly prevented the recurrence of colorectal adenomas. A minimum effective amount of green tea catechins for cancer prevention was found in humans. In addition, the combination of green tea catechins and anticancer drugs engendered a new cancer therapeutic strategy.

Conclusion

The consumption of 10 Japanese-size cups of green tea per day is a significant factor in primary cancer prevention for the general population, and the preventive effect on recurrence of colorectal adenomas in patients is vital evidence in tertiary cancer prevention.

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References

  • Adachi S, Nagao T, Ingolfsson HI, Maxfield FR, Andersen OS, Kopelovich L, Weinstein IB (2007) The inhibitory effect of (−)-epigallocatechin gallate on activation of the epidermal growth factor receptor is associated with altered lipid order in HT29 colon cancer cells. Cancer Res 67:6493–6501

    Article  PubMed  CAS  Google Scholar 

  • Ahmad N, Feyes DK, Nieminen AL, Agarwal R, Mukhtar H (1997) Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J Natl Cancer Inst 89:1881–1886

    Article  PubMed  CAS  Google Scholar 

  • Ben-Neriah Y, Karin M (2011) Inflammation meets cancer, with NF-κB as the matchmaker. Nat Immunol 12:715–723

    Article  PubMed  CAS  Google Scholar 

  • Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A (2006) Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res 66:1234–1240

    Article  PubMed  CAS  Google Scholar 

  • Chen W, Dong Z, Valcic S, Timmermann BN, Bowden GT (1999) Inhibition of ultraviolet B-induced c-fos gene expression and p38 mitogen-activated protein kinase activation by (−)-epigallocatechin gallate in a human keratinocyte cell line. Mol Carcinog 24:79–84

    Article  PubMed  CAS  Google Scholar 

  • Conney AH, Wang ZY, Huang MT, Ho CT, Yang CS (1992) Inhibitory effect of oral administration of green tea on tumorigenesis by ultraviolet light, 12-O-tetra decanoylphorbol-13-acetate and N-nitrosodiethylamine in mice. CRC Press, Boca Raton, pp 361–373

    Google Scholar 

  • El-Deiry WS, Harper JW, O’Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, Wiman KG, Mercer WE, Kastan MB, Kohn KW, Elledge SJ, Kinzler KW, Vogelstein B (1994) WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 54:1169–1174

    PubMed  CAS  Google Scholar 

  • Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N, other National Surgical Adjivant Breast and Bowel Project Inverstigators (1998) Tamoxifen for prevention of breast cancer. Report of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 90:1371–1388

    Article  PubMed  CAS  Google Scholar 

  • Fujiki H (1999) Two stages of cancer prevention with green tea. J Cancer Res Clin Oncol 125:589–597

    Article  PubMed  CAS  Google Scholar 

  • Fujiki H (2005) Green tea: health benefits as cancer preventive for humans. Chem Rec 5:119–132

    Article  PubMed  CAS  Google Scholar 

  • Fujiki H, Okuda T (1992) (−)-Epigallocatechin gallate. Drugs Future 17:462–464

    Google Scholar 

  • Fujiki H, Suganuma M (2002) Green tea and cancer prevention. Proc Jpn Acad 78(B):263–270

    Article  Google Scholar 

  • Fujiki H, Suganuma M (2011) Tumor promoters-microcystin-LR, nodularin and TNF-α and human cancer development. Anticancer Agents Med Chem 11:4–18

    Article  PubMed  CAS  Google Scholar 

  • Fujiki H, Suganuma M, Okabe S, Komori A, Sueoka E, Sueoka N, Kozu T, Sakai Y (1996) Japanese green tea as a cancer preventive in humans. Nutr Rev 54:S67–S70

    Article  PubMed  CAS  Google Scholar 

  • Fujiki H, Suganuma M, Okabe S, Sueoka E, Sueoka N, Fujimoto N, Goto Y, Matsuyama S, Imai K, Nakachi K (2001) Cancer prevention with green tea and monitoring by a new biomarker, hnRNP B1. Mutat Res 480–481:299–304

    PubMed  Google Scholar 

  • Fujiki H, Suganuma M, Imai K, Nakachi K (2002) Green tea: cancer preventive beverage and/or drug. Cancer Lett 188:9–13

    Article  PubMed  CAS  Google Scholar 

  • Fujiki H, Takeuchi H, Nishitani N, Yamanaka H, Suzuki K, Kurusu M, Suganuma M (2004) Carcinogenic potential of tobacco tar-resistant Staphylococcus aureus in buccal cavity. J Cancer Res Clin Oncol 130:301–305

    Article  PubMed  CAS  Google Scholar 

  • Fujita Y, Yamane T, Tanaka M, Kuwata K, Okuzumi J, Takahashi T, Fujiki H, Okuda T (1989) Inhibitory effect of (−)-epigallocatechin gallate on carcinogenesis with N-ethyl-N’-nitro-N-nitrosoguanidine in mouse duodenum. Jpn J Cancer Res 80:503–505

    Article  PubMed  CAS  Google Scholar 

  • Gupta S, Hastak K, Ahmad N, Lewin JS, Mukhtar H (2001) Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc Natl Acad Sci USA 98:10350–10355

    Article  PubMed  CAS  Google Scholar 

  • Hecker E, Adolf W, Hergenhahn R, Schmidt R, Sorg B (1984) Irritant diterpene ester promoters of mouse skin: contributions to etiologies of environmental cancer and to biochemical mechanisms of carcinogenesis. In: Fujiki H, Hecker E, Moore RE, Sugimura T, Weinstein IB (eds) Cellular interactions by environmental tumor promoters. Jpn Sci Soc Press/VNU Science Press, BV, Tokyo/Utrecht, pp 3–36

    Google Scholar 

  • Imai K, Suga K, Nakachi K (1997) Cancer-preventive effects of drinking green tea among a Japanese population. Prev Med 26:769–775

    Article  PubMed  CAS  Google Scholar 

  • Iwasaki M, Inoue M, Sasazuki S, Sawada N, Yamaji T, Shimazu T, Willett WC, Tsugane S (2010) Green tea drinking and subsequent risk of breast cancer in a population to based cohort of Japanese women. Breast Cancer Res 12:R88. (Epub ahead of print)

    Google Scholar 

  • Komori A, Yatsunami J, Okabe S, Abe S, Hara K, Suganuma M, Kim SJ, Fujiki H (1993a) Anticarcinogenic activity of green tea polyphenols. Jpn J Clin Oncol 23:186–190

    PubMed  CAS  Google Scholar 

  • Komori A, Yatsunami J, Suganuma M, Okabe S, Abe S, Sakai A, Sasaki K, Fujiki H (1993b) Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation. Cancer Res 53:1982–1985

    PubMed  CAS  Google Scholar 

  • Kuzuhara T, Sei Y, Yamaguchi K, Suganuma M, Fujiki H (2006) DNA and RNA as new binding targets of green tea catechins. J Biol Chem 281:17446–17456

    Article  PubMed  CAS  Google Scholar 

  • Kuzuhara T, Tanabe A, Sei Y, Yamaguchi K, Suganuma M, Fujiki H (2007a) Synergistic effects of multiple treatments, and both DNA and RNA direct bindings on, green tea catechins. Mol Carcinog 46:640–645

    Article  PubMed  CAS  Google Scholar 

  • Kuzuhara T, Suganuma M, Kurusu M, Fujiki H (2007b) Helicobacter pylori-secreting protein Tipα is a potent inducer of chemokine gene expressions in stomach cancer cells. J Cancer Res Clin Oncol 133:287–296

    Article  PubMed  CAS  Google Scholar 

  • Kuzuhara T, Suganuma M, Fujiki H (2008) Green tea catechin as a chemical chaperone in cancer prevention. Cancer Lett 261:12–20

    Article  PubMed  CAS  Google Scholar 

  • Laurie SA, Miller VA, Grant SC, Kris MG, Ng KK (2005) Phase 1 study of green tea extract in patients with advanced lung cancer. Cancer Chemother Pharmacol 55:33–38

    Article  PubMed  Google Scholar 

  • Nakachi K, Suemasu K, Suga K, Takeo T, Imai K, Higashi Y (1998) Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res 89:254–261

    Article  PubMed  CAS  Google Scholar 

  • Nakachi K, Matsuyama S, Miyake S, Suganuma M, Imai K (2000) Preventive effects of drinking green tea on cancer and cardiovascular disease: epidemiological evidence for multiple targeting prevention. BioFactors 13:49–54

    Article  PubMed  CAS  Google Scholar 

  • Narisawa T, Fukaura Y (1993) 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 84:1007–1009

    Article  PubMed  CAS  Google Scholar 

  • NCI, Dcpc, Chemoprevention Branch and Agent Development Committee (1996) Clinical development plan:tea extracts green tea polyphenols epigallocatechin gallate. J Cell Biochem 26S:236–257

    Google Scholar 

  • Nishida H, Omori M, Fukutomi Y, Ninomiya M, Nishiwaki S, Suganuma M, Moriwaki H, Muto Y (1994) Inhibitory effects of (−)-epigallocatechin gallate on spontaneous hepatoma in C3H/HeNCrj mice and human hepatoma-derived PCL/PRF/5 cells. Jpn J Cancer Res 85:221–225

    Article  PubMed  CAS  Google Scholar 

  • Novoa I, Zeng H, Harding HP, Ron D (2001) Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2α. J Cell Biol 153:1011–1022

    Article  PubMed  CAS  Google Scholar 

  • Ogunleye AA, Xue F, Michels KB (2010) Green tea consumption and breast cancer risk or recurrence: a meta-analysis. Breast Cancer Res Treat 119:477–484

    Article  PubMed  Google Scholar 

  • Okabe S, Suganuma M, Hayashi M, Sueoka E, Komori A, Fujiki H (1997) Mechanisms of growth inhibition of human lung cancer cell line, PC-9, by tea polyphenols. Jpn J Cancer Res 88:639–643

    Article  PubMed  CAS  Google Scholar 

  • Okabe S, Ochiai Y, Aida M, Park K, Kim SJ, Nomura T, Suganuma M, Fujiki H (1999) Mechanistic aspects of green tea as a cancer preventive: effect of components on human stomach cancer cell lines. Jpn J Cancer Res 90:733–739

    Article  PubMed  CAS  Google Scholar 

  • Okabe S, Fujimoto N, Sueoka N, Suganuma M, Fujiki H (2001) Modulation of gene expression by (−)-epigallocatechin gallate in PC-9 cells using a cDNA expression array. Biol Pharm Bull (Tokyo) 24:883–886

    Article  CAS  Google Scholar 

  • Okuda T, Mori K, Hayatsu H (1984) Inhibitory effect of tannins on direct-acting mutagens. Chem Pharm Bull (Tokyo) 32:3755–3758

    Article  CAS  Google Scholar 

  • Okuda T, Mori K, Hatano T (1985) Relationship of the structure of tannins to the binding activities with hemoglobin and methylene blue. Chem Pharm Bull (Tokyo) 33:1424–1433

    Article  CAS  Google Scholar 

  • Pisters KM, Newman RA, Coldman B, Shin DM, Khuri FR, Hong WK, Glisson BS, Lee JS (2001) Phase 1 trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol 19:1830–1838

    PubMed  CAS  Google Scholar 

  • Shimizu M, Fukutomi Y, Ninomiya M, Nagura K, Kato T, Araki H, Suganuma M, Fujiki H, Moriwaki H (2008) Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study. Cancer Epidemiol Biomarkers Prev 17:3020–3025

    Article  PubMed  CAS  Google Scholar 

  • Shimizu M, Adachi S, Masuda M, Kozawa O, Moriwaki H (2011) Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases. Mol Nutr Food Res 55:832–843

    Article  PubMed  CAS  Google Scholar 

  • Sporn MB, Dunlop NM, Newton DL, Smith JM (1976) Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc 35:1332–1338

    PubMed  CAS  Google Scholar 

  • Stingl JC, Ettrich T, Muche R, Wiedom M, Brockmöller J, Seeringer A, Seufferlein T (2011) Protocol for minimizing the risk of metachronous adenomas of the colorectum with green tea extract (MIRACLE): a randomized controlled trial of green tea extract versus placebo for nutriprevention of metachronous colon adenomas in the elderly population. BMC Cancer 11:360

    Article  PubMed  CAS  Google Scholar 

  • Sueoka N, Suganuma M, Sueoka E, Okabe S, Matsuyama S, Imai K, Nakachi K, Fujiki H (2001) A new function of green tea: prevention of lifestyle-related diseases. Ann N Y Acad Sci 928:274–280

    Article  PubMed  CAS  Google Scholar 

  • Suganuma M, Fujiki H, Suguri H, Yoshizawa S, Hirota M, Nakayasu M, Ojika M, Wakamatsu K, Yamada K, Sugimura T (1988) Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter. Proc Natl Acad Sci USA 85:1768–1771

    Article  PubMed  CAS  Google Scholar 

  • Suganuma M, Okabe S, Oniyama M, Tada Y, Ito H, Fujiki H (1998) Wide distribution of [3H](−)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis 19:1771–1776

    Article  PubMed  CAS  Google Scholar 

  • Suganuma M, Okabe S, Kai Y, Sueoka N, Sueoka E, Fujiki H (1999a) Synergistic effects of (−)-epigallocatechin gallate with (−)-epicatechin, sulindac, or tamoxifen on cancer-preventive activity in the human lung cancer cell line PC-9. Cancer Res 59:44–47

    PubMed  CAS  Google Scholar 

  • Suganuma M, Okabe S, Marino MW, Sakai A, Sueoka E, Fujiki H (1999b) Essential role of tumor necrosis factor α (TNF-α) in tumor promotion as revealed by TNF-α-deficient mice. Cancer Res 59:4516–4518

    PubMed  CAS  Google Scholar 

  • Suganuma M, Ohkura Y, Okabe S, Fujiki H (2001) Combination cancer chemoprevention with green tea extract and sulindac shown in intestinal tumor formation in Min mice. J Cancer Res Clin Oncol 127:69–72

    Article  PubMed  CAS  Google Scholar 

  • Suganuma M, Okabe S, Kurusu M, Iida N, Ohshima S, Saeki Y, Kishimoto T, Fujiki H (2002) Discrete roles of cytokines, TNF-α, IL-1, IL-6 in tumor promotion and cell transformation. Int J Oncol 20:131–136

    PubMed  CAS  Google Scholar 

  • Suganuma M, Kurusu M, Suzuki K, Tasaki E, Fujiki H (2006) Green tea polyphenol stimulates cancer preventive effects of celecoxib in human lung cancer cells by upregulation of GADD153 gene. Int J Cancer 119:33–40

    Article  PubMed  CAS  Google Scholar 

  • Suganuma M, Saha A, Fujiki H (2011) New cancer treatment strategy using combination of green tea catechins and anticancer drugs. Cancer Sci 102:317–323

    Article  PubMed  CAS  Google Scholar 

  • Taniguchi S, Fujiki H, Kobayashi H, Go H, Miyado K, Sadano H, Shimokawa R (1992) Effect of (−)-epigallocatechin gallate, the main constituent of green tea, on lung metastasis with mouse B16 melanoma cell lines. Cancer Lett 65:51–54

    Article  PubMed  CAS  Google Scholar 

  • Tsao AS, Liu D, Martin J, Tang X-m, Lee JJ, El-Naggar AK, Wistuba I, Culotta KS, Mao L, Gillenwater A, Sagesaka YM, Hong WK, Papadimitrakopoulou V (2009) Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions. Cancer Rev Res 2:931–941

    CAS  Google Scholar 

  • Tsubono Y, Nishino Y, Komatsu S, Hsieh C–C, Kanemura S, Tsuji I, Nakatsuka H, Fukao A, Satoh H, Hisamichi S (2001) Green tea and the risk of gastric cancer in Japan. N Engl J Med 344:632–636

    Article  PubMed  CAS  Google Scholar 

  • Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smith AMM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532

    Article  PubMed  CAS  Google Scholar 

  • Wang ZY, Hong JY, Huang MT, Reuhl K, Conney AH, Yang CS (1992) 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 52:1943–1947

    PubMed  CAS  Google Scholar 

  • Yamane T, Hagiwara N, Tateishi M, Akachi S, Kim M, Okuzumi J, Kitao Y, Inagake M, Kuwata K, Takahashi T (1991) Inhibition of azoxymethane-induced colon carcinogenesis in rat by green tea polyphenol fraction. Jpn J Cancer Res 82:1336–1339

    Article  PubMed  CAS  Google Scholar 

  • Yamane T, Takahashi T, Kuwata K, Oya K, Inagake M, Kitao Y, Suganuma M, Fujiki H (1995) Inhibition of N-methyl-N’-nitro-N-nitrosoguanidine-induced carcinogenesis by (−)-epigallocatechin gallate in the rat glandular stomach. Cancer Res 55:2081–2084

    PubMed  CAS  Google Scholar 

  • Yang CS, Wang ZY (1993) Tea and cancer. J Natl Cancer Inst 85:1038–1049

    Article  PubMed  CAS  Google Scholar 

  • Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS (1998) Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis 19:611–616

    Article  PubMed  CAS  Google Scholar 

  • Yoshizawa S, Horiuchi T, Fujiki H, Yoshida T, Okuda T, Sugimura T (1987) Antitumor promoting activity of (−)-epigallocatechin gallate, the main constituent of “tannin” in green tea. Phytother Res 1:44–47

    Article  CAS  Google Scholar 

  • Yoshizawa S, Horiuchi T, Suganuma M, Nishiwaki S, Yatsunami J, Okabe S, Okuda T, Muto Y, Frenkel K, Troll W, Fujiki H (1992) Penta-O-galloyl-β-d-glucose and (−)-epigallocatechin gallate. Am Chem Soc:316–325

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Acknowledgments

To Prof. Erich Hecker, we express gratitude for his fruitful discussion. We thank Prof. Takuo Okuda for providing numerous polyphenols including (−)-epigallocatechin gallate (EGCG) and penta-O-galloyl-β-d-glucose (5GG), Prof. Takashi Sugimura for his encouragement during the course of this work, and our Japanese colleagues cited in our references for their research. This work was supported by Japan Society for the Promotion of Science: Scientific Research on Priority Areas for Cancer Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan; Comprehensive Research on Aging and Health; and Cancer Research from the Ministry of Health, Labor, and Welfare, Japan; Selective Applied and Developed Research, and Green Tea Extracts Research Development for Cancer Prevention by the Department of Agriculture and Forests and the Department of Health and Human Services of Saitama Prefecture, Japan; and the Smoking Research Fund.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, 770-8514, Japan

    Hirota Fujiki

  2. Department of Radiobiology and Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, 732-0815, Japan

    Kazue Imai & Kei Nakachi

  3. Department of Medicine, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan

    Masahito Shimizu & Hisataka Moriwaki

  4. Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, 362-0806, Japan

    Masami Suganuma

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  1. Hirota Fujiki
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  2. Kazue Imai
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  3. Kei Nakachi
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  4. Masahito Shimizu
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  5. Hisataka Moriwaki
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  6. Masami Suganuma
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Correspondence to Hirota Fujiki.

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Fujiki, H., Imai, K., Nakachi, K. et al. Challenging the effectiveness of green tea in primary and tertiary cancer prevention. J Cancer Res Clin Oncol 138, 1259–1270 (2012). https://doi.org/10.1007/s00432-012-1250-y

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