Skip to main content
PMC home page
Cancer Science logoLink to Cancer Science
. 2005 Aug 19;95(7):596–601. doi: 10.1111/j.1349-7006.2004.tb02493.x

HTLV‐1 provirus load in peripheral blood lymphocytes of HTLV‐1 carriers is diminished by green tea drinking

Junichiro Sonoda 1,2, Chihaya Koriyama 3, Shinako Yamamoto 4, Tomohiro Kozako 1, Hong Chuan Li 2, Carolina Lema 2, Shinji Yashiki 2, Toshinobu Fujiyoshi 2, Mitsuhiro Yoshinaga 4, Yukihiro Nagata 4, Suminori Akiba 3, Toshiro Takezaki 5, Katsushi Yamada 1, Shunro Sonoda 2,5,✉
PMCID: PMC11158836  PMID: 15245597

Abstract

Human T‐cell lymphotropic virus type 1 (HTLV‐1) is causatively associated with adult T‐cell leukemia (ATL) and HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since a high level of HTLV‐1 provirus load in circulating lymphocytes is thought to be a risk for ATL and HAM/TSP, diminution of HTLV‐1 provirus load in the circulation may prevent these intractable diseases. Our previous study (Jpn J Cancer Res 2000; 91: 34–40) demonstrated that green tea polyphenols inhibit in vitro growth of ATL cells, as well as HTLV‐1‐infected T‐cells. The present study aimed to investigate the in vivo effect of green tea polyphenols on HTLV‐1 provirus load in peripheral blood lymphocytes on HTLV‐1 carriers. We recruited 83 asymptomatic HTLV‐1 carriers to examine HTLV‐1 provirus DNA with or without administration of capsulated green tea extract powder. Thirty‐seven subjects were followed up for 5 months by measuring HTLV‐1 provirus load after daily intake of 9 capsules of green tea extract powder per day (equivalent to 10 cups of regular green tea), and 46 subjects lived ad libitum without intake of any green tea capsule. The real‐time PCR quantification of HTLV‐1 DNA revealed a wide range of variation of HTLV‐1 provirus load among asymptomatic HTLV‐1 carriers (0.2‐200.2 copies of HTLV‐1 provirus load per 1000 peripheral blood lymphocytes). Daily intake of the capsulated green tea for 5 months significantly diminished the HTLV‐1 provirus load as compared with the controls (P=0.031). These results suggest that green tea drinking suppresses proliferation of HTLV‐1‐infected lymphocytes in vivo.

References

  • 1. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. Adult T‐cell leukemia: clinical and hematologic features of 16 cases. Blood 1977; 50: 481–92. [PubMed] [Google Scholar]
  • 2. Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, Shirakawa S, Miyoshi I. Adult T‐cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci USA 1981; 78: 6476–80. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M. HTLV‐I associated myelopathy, a new clinical entity. Lancet 1986; i: 1031–2. [DOI] [PubMed] [Google Scholar]
  • 4. Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A. The G. Antibodies to human T‐lymphotropic virus type‐I in patients with tropical spastic paraparesis. Lancet 1985; ii: 407–10. [DOI] [PubMed] [Google Scholar]
  • 5. Hino S, Katamine S, Miyata H, Tsuji Y, Yamabe T, Miyamoto T. Primary prevention of HTLV‐1 in Japan. Leukemia 1997; Suppl 3: 57–9. [PubMed] [Google Scholar]
  • 6. Takahashi K, Takezaki T, Oki T, Kawakami K, Yashiki S, Fujiyoshi T, Usuku K, Mueller N, Osame M, Miyata K, Nagata Y, Sonoda S. The Mother‐to‐Child Transmission Study Group. Inhibitory effect of maternal antibody on mother‐to‐child transmission of human T‐lymphotropic virus type I. Int J Cancer 1991; 49: 673–7. [DOI] [PubMed] [Google Scholar]
  • 7. Taylor GP, Tosswill JH, Matutes E, Daenke S, Hall S, Bain BJ, Davis R, Thomas D, Rossor M, Bangham CR, Weber JN. Prospective study of HTLV‐I infection in an initially asymptomatic cohort. J Acquir Immune Defic Syndr 1999; 22: 92–100. [DOI] [PubMed] [Google Scholar]
  • 8. Hisada M, Okayama A, Shioiri S, Spiegelman DL, Stuver SO, Mueller NE. Risk factors for adult T‐cell leukemia among carriers of human T‐lymphotropic virus type I. Blood 1998; 92: 3557–61. [PubMed] [Google Scholar]
  • 9. Manns A, Miley WJ, Wilks RJ, Morgan OS, Hanchard B, Wharfe G, Cranston B, Maloney E, Wells SL, Blattner WA, Waters D. Quantitative proviral DNA and antibody levels in the natural history of HTLV‐I infection. J Infect Dis 1999; 180: 1487–93. [DOI] [PubMed] [Google Scholar]
  • 10. Okayama A, Stuver SO. Long‐term follow‐up of HTLV‐1 carriers. In: Two decades of adult T‐cell leukemia and HTLV‐1 research. Gann Monogr 2003; 50: 127–39. [Google Scholar]
  • 11. Rice‐Evans C. Implications of the mechanisms of action of tea polyphenols as antioxidants in vitro for chemoprevention in humans. Proc Soc Exp Biol Med 1999; 220: 262–6. [DOI] [PubMed] [Google Scholar]
  • 12. Wiseman SA, Balentine DA, Frei B. Antioxidants in tea. Crit Rev Food Sci Nutr 1997; 37: 705–18. [DOI] [PubMed] [Google Scholar]
  • 13. Muto S, Yokoi T, Gondo Y, Katsuki M, Shioyama Y, Fujita K, Kamataki T. Inhibition of benzo[a]pyrene‐induced mutagenesis by (‐)‐epigallocatechin gallate in the lung of rpsL‐transgenic mice. Carcinogenesis 1999; 20: 421–4. [DOI] [PubMed] [Google Scholar]
  • 14. Kuroda Y, Kara Y. Antimutagenic and anticarcinogenic activity of tea polyphenols. Mutat Res 1999; 436: 69–97. [DOI] [PubMed] [Google Scholar]
  • 15. Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS. Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis 1998; 19: 611–6. [DOI] [PubMed] [Google Scholar]
  • 16. Okabe S, Ochiai Y, Aida M, Park K, Kim S‐J, Nomura T, Suganuma M, Fujiki H. Mechanistic aspects of green tea as a cancer preventive: effect of components on human stomach cancer cell lines. Jpn J Cancer Res 1999; 90: 733–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Setiawan VW, Zhang ZF, Yu GP, Lu QY, Li YL, Lu ML, Wang MR, Guo CH, Yu SZ, Kurtz RC, Hsieh CC. Protective effect of green tea on the risks of chronic gastritis and stomach cancer. Int J Cancer 2001; 92: 600–4. [DOI] [PubMed] [Google Scholar]
  • 18. Rao DN, Ganesh B, Dinshaw KA, Mohandas KM. A case‐control study of stomach cancer in Mumbai, India. Int J Cancer 2002; 99: 727–31. [DOI] [PubMed] [Google Scholar]
  • 19. 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; 79: 1067–74. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Ohno Y, Wakai K, Genka K, Ohmine K, Kawamura T, Tamakoshi A, Aoki R, Senda M, Hayashi Y, Nagao K, Fukuma S, Aoki K. Tea consumption and lung cancer risk: a case‐control study in Okinawa, Japan. Jpn J Cancer Res 1995; 86: 1027–34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Imai K, Suga K, Nakachi K. Cancer‐preventive effects of drinking green tea among a Japanese population. Prev Med 1997; 26: 769–75. [DOI] [PubMed] [Google Scholar]
  • 22. Li H‐C, Yashiki S, Sonoda J, Lou H, Ghosh SK, Byrnes JJ, Lema C, Fujiyoshi T, Karasuyama M, Sonoda S. Green tea polyphenols induce apoptosis in vitro in peripheral blood T lymphocytes of adult T‐cell leukemia patients. Jpn J Cancer Res 2000; 91: 34–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Miyoshi I, Kubonishi I, Yoshimoto S, Shiraishi Y. A T‐cell line derived from normal human cord leukocytes by co‐culturing with human leukemic T‐cells. Gann 1981; 72: 978–81. [PubMed] [Google Scholar]
  • 24. Ehrlich G, Greenberg S, Abbot M. Detection of human T‐cell lymphoma/ leukemia viruses. In: Innis M, Gelfand D, Sninsky J, White T, editors PCR protocols. San Diego : Academic Press; 1990. p. 325–32. [Google Scholar]
  • 25. Pisters KM, Newman RA, Goldman B, Shin DM, Khuri FR, Hong WK, Glisson BS, Lee JS. Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol 2001; 19: 1830–8. [DOI] [PubMed] [Google Scholar]
  • 26. Nagai M, Usuku K, Matsumoto W, Kodama D, Takenouchi N, Moritoyo T, Hashiguchi S, Ichinose M, Bangham CRM, Izumo S, Osame M. Analysis of HTLV‐1 proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV‐1 carriers: high proviral load strongly predisposes to HAM/TSP. J Neurovirol 1998; 4: 586–93. [DOI] [PubMed] [Google Scholar]
  • 27. Yang CS, Chen L, Lee MJ, Balentine D, Kuo MC, Schantz SP. Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers. Cancer Epidemiol Biomarkers Prev 1998; 7: 351–4. [PubMed] [Google Scholar]
  • 28. Mueller N, Okayama A, Stuver S, Tachibana N. Findings from the Miyazaki Cohort Study. J Acquir Immune Defic Syndr Hum Retrovirol 1996; 13: S2–7. [DOI] [PubMed] [Google Scholar]
  • 29. Hisada M, Okayama A, Tachibana N, Stuver SO, Spiegelman DL, Tsubouchi H, Mueller NE. Predictors of level of circulating abnormal lymphocytes among human T‐lymphotropic virus type I carriers in Japan. Int J Cancer 1998; 77: 188–92. [DOI] [PubMed] [Google Scholar]
  • 30. Lee MJ, Wang ZY, Li H, Chen L, Sun Y, Gobbo S, Balentine DA, Yang CS. Analysis of plasma and urinary tea polyphenols in human subjects. Cancer Epidemiol Biomarkers Prev 1995; 4: 393–9. [PubMed] [Google Scholar]
  • 31. Ahmad N, Gupta S, Mukhtar H. Green tea polyphenol epigallocatechin‐3‐gallate differentially modulates nuclear factor kappaB in cancer cells versus normal cells. Arch Biochem Biophys 2000; 376: 338–46. [DOI] [PubMed] [Google Scholar]
  • 32. Suzuki T, Hirai H, Murakami T, Yoshida M. Tax protein of HTLV‐1 destabilizes the complexes of NF‐kappa B and I kappa B‐alpha and induces nuclear translocation of NF‐kappa B for transcriptional activation. Oncogene 1995; 10: 1199–207. [PubMed] [Google Scholar]
  • 33. Yamaguchi K, Kiyokawa T, Nakada K, Yul LS, Asou N, Ishii T, Sanada I, Seiki M, Yoshida M, Matutes E. Polyclonal integration of HTLV‐I proviral DNA in lymphocytes from HTLV‐I sero‐positive individuals: an intermediate state between the healthy carrier state and smoldering ATL. Br J Haema-tol 1988; 68: 169–74. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Science are provided here courtesy of Wiley

RESOURCES