Medical Oncology

, Volume 25, Issue 1, pp 30–39

Epigallocatechin-3-gallate induces apoptosis and cell cycle arrest in HTLV-1-positive and -negative leukemia cells

  • S. Harakeh
  • K. Abu-El-Ardat
  • M. Diab-Assaf
  • A. Niedzwiecki
  • M. El-Sabban
  • M. Rath
Original Paper

Abstract

The objective of this study is to evaluate the efficacy of epigallocatechin gallate against ATL cells. The anti-proliferative and pro-apoptotic effects of EGCG were evaluated in HTLV-1-positive and -negative cells. EGCG exhibited a marked decrease in proliferation of ATL cells at 96 h of treatment. The results indicated that TGF-α was down-regulated whereas levels of TGF-β2 increased. Cell cycle distribution analysis revealed an increase in cells in the pre-G1 phase which was confirmed by ELISA. The results on proteins showed an up-regulation of p53, Bax and p21 protein levels while the levels of Bcl-2α were down-regulated.

Keywords

Apoptosis Human T-cell Lymphotrophic Virus-1 (HTLV-1) Epigallocatechin-3-gallate (EGCG) p53 p21 Transforming Growth Factor (TGF) 

References

  1. 1.
    Hare Y. Green tea: health benefits and applications. New York: Marcel Dekker, Basel; 2001.Google Scholar
  2. 2.
    Erba D, Riso P, Colombo A, Testolin G. Supplementation of Jurkat T cells with green tea extract decreases oxidative damage due to iron treatment. J Nutr 1999;129:2130–4.PubMedGoogle Scholar
  3. 3.
    Kawai K, et al. Epigallocatechin gallate, the main component of tea polyphenol, binds to CD4 and interferes with gp 120 binding. J Allergy Clin Immunol 2003;112:951–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Hayakawa S, et al. Apoptosis induction by epigallocatechin gallate involves its binding to Fas. Biochem Biophys Res Commun 2001;285:1102–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Ahmad N, Gupta S, Mukhtar H. Green tea polyphenol epigallocatechin-3-gallate differentially modulates nuclear factor κB in cancer cells versus normal cells. Arch Biochem Biophys 2000;376:338–46.PubMedCrossRefGoogle Scholar
  6. 6.
    Gupta S, Ahmad N, Nieminen AL, Mukhtar H. Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (-)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. Toxicol Appl Pharmacol 2000;164:82–90.PubMedCrossRefGoogle Scholar
  7. 7.
    Fujiki HJ, et al. Cancer inhibition by green tea. Mutation Res 1998;402:307–10.PubMedGoogle Scholar
  8. 8.
    Wang YC, Bachrach U. The specific anti-cancer activity of green tea (-)-epigallocatechin-3-gallate (EGCG). Amino Acids 2002;22:131–43.PubMedCrossRefGoogle Scholar
  9. 9.
    Li H, et al. 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.PubMedGoogle Scholar
  10. 10.
    Roy M, Chakrabarty S, Sinha D, Bhattacharya R, Siddiqi M. Anticlastogenic, antigenotoxic and apoptotic activity of epigallocatechin gallate: a green tea polyphenol. Mutation Res 2003;523–524:33–41.PubMedGoogle Scholar
  11. 11.
    Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. Antitumor effect of nutrient synergy on human osteosarcoma cells U-2OS, MNNG-HOS and Ewing’s Sarcoma SK-ES.1. Oncol Rep 2005;13:253–7.PubMedGoogle Scholar
  12. 12.
    Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human prostate cancer PC-3 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry. In Vivo 2005;19:179–83.PubMedGoogle Scholar
  13. 13.
    Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. In vitro and in vivo antitumorigenic activity of a mixture of lysine, proline, acorbic acid, and green tea extract on human breast cancer lines MDA-MB-231 and MCF-7. Med Oncol 2005;22:129–38.PubMedCrossRefGoogle Scholar
  14. 14.
    Hinuma Y, et al. Transforming genes in human leukemia cells. PNAS 1985;66:1371–8.Google Scholar
  15. 15.
    Kaplan J, Khabbaz R. The epidemiology of human T-lymphotropic virus type I and II. Med Virol 1993;3:137–48.CrossRefGoogle Scholar
  16. 16.
    Gessain A. Epidemiology of HTLV-1 and associated diseases. In: Höllsberg P, Hafler DA, editors. Human T-cell lymphotropic virus type 1. John Willey & Sons Ltd.; 1996. p. 33–64.Google Scholar
  17. 17.
    Hermine O, et al. Brief report: treatment of adult T-cell leukemia-lymphoma with zidovudine and interferon alpha. N Engl J Med 1995;332:1749–51.PubMedCrossRefGoogle Scholar
  18. 18.
    Macchi B, Faraoni I, Zhang J, Grelli S, Favalli C, Mastino A, et al. AZT inhibits the transmission of human T cell leukemia/lymphoma virus type I to adult peripheral blood mononuclear cells in vitro. J Gen Virol 1997;78:1007–16.PubMedGoogle Scholar
  19. 19.
    Zhang J, Balestrieri E, Grelli S, Matteucci C, Pagnini V, D’Agostini C, et al. Efficacy of 3′-azido 3′deoxythymidine (AZT) in preventing HTLV-1 transmission to human cord blood mononuclear cells. Virus Res 2001;78:67–78.PubMedCrossRefGoogle Scholar
  20. 20.
    Bazarbachi A, Hermine O. Treatment with a combination of zidovudine and alpha-interferon in naïve and pretreated adult T-cell leukemia/lymphoma patients. J Acq Immun Defic Synd Hum 1996;R13(Suppl. 1):5186–90.Google Scholar
  21. 21.
    Hsu TC, et al. Comparative efficacy as antioxidants between ascorbic acid and epigallocatechin gallate on cells of two human lymphoblastoid lines. Cancer Genet Cytogenet 2001;124:169–71.PubMedCrossRefGoogle Scholar
  22. 22.
    Mitscher LA, et al. Chemoprotection: a review of the potential therapeutic antioxidant properties of green tea (Camellia sinensis) and certain of its constituents. Med Res Rev 1997;17:327–65.PubMedCrossRefGoogle Scholar
  23. 23.
    Yang CS, Yang GY, Landau JM, Kim S, Liao J. Exp Lung Res 1998;24:629.Google Scholar
  24. 24.
    Otsuka T, et al. Growth inhibition of leukemic cells by (-)-epigallocatechin gallate: the main constituent of green tea. Life Sci 1998;63:1397–403.PubMedCrossRefGoogle Scholar
  25. 25.
    Gupta S, Hussain T, Mukhtar H. Molecular pathway for (-)-epigallocatechin-3-gallate induced cell cycle arrest and apoptosis of human prostate carcinoma cells. Arch Biochem Biophys 2003;410:177–85.PubMedCrossRefGoogle Scholar
  26. 26.
    Kanai M, et al. TGF-α inhibits apoptosis of murine gastric pit cells through an NF-κB-dependent pathway. Gastroenterology 2001;121:56–67.PubMedCrossRefGoogle Scholar
  27. 27.
    Javelaud D, Mauviel A. Mammalian transforming growth factors-βs: Smad signaling and physio-pathalogical roles. Int J Biochem Cell Biol 2004;36:1161–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Lee DK, et al. The human papilloma virus E7 oncoprotein inhibits transforming growth factor-β signaling by blocking binding of the Smad complex to its target sequence. J Biol Chem 2002;277:38557–64.PubMedCrossRefGoogle Scholar
  29. 29.
    Saeki K, et al. Cell density-dependent apoptosis in HL-60 cells, which is mediated by an unknown soluble factor, is inhibited by transforming growth factor beta 1 and overexpression of Bcl-2. J Biol Chem 2000;272:3–10.Google Scholar
  30. 30.
    Cerwenka A, Kovar H, Majdic O, Holter W. Fas- and activation-induced apoptosis are reduced in human T cells preactivated in the presence of TGF-beta 1. J Immunol 1996;156:459–64.PubMedGoogle Scholar
  31. 31.
    Chen W, Jin W, Wahl SM. Engagement of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) induces transforming growth factor β (TGF-β) production by murine CD4+ T cells. J Exp Med 1998;188:1849–57.PubMedCrossRefGoogle Scholar
  32. 32.
    Patil S, et al. Smad7 is induced by CD40 and protects WEHI 231 B-lymphocytes from transforming growth factor-β-induced growth inhibition and apoptosis. J Biol Chem 2000;275:38363–70.PubMedCrossRefGoogle Scholar
  33. 33.
    Inmann GJ, Allday MJ. Apoptosis induced by TGF-β1 in Burkitt’s Lymphoma cells is caspase 8 dependent but is death receptor independent. J Immunol 2000;165:2500–10.Google Scholar
  34. 34.
    Wolfraim LA, Walz TM, James Z, Fernandez T, Letterio JJ. p21Cip1 and p27Kip1 act in synergy of naïve T cells to TGF-beta-mediated G1 arrest through modulation of IL-2 responsiveness. J Immunol 2004;173:3093–102.PubMedGoogle Scholar
  35. 35.
    Sánchez-Capelo A. Dual role for TGF-β1 in apoptosis. Cytokine Growth Factor Rev 2005;16:15–34.PubMedCrossRefGoogle Scholar
  36. 36.
    Arnulf B, et al. Human T-cell lymphotropic virus oncoprotein tax represses TGF-β1 signaling in human T cells Via c-Jun activation: a potential mechanism of HTLV-I leukemogenesis. Blood 2002;100:4129–37.PubMedCrossRefGoogle Scholar
  37. 37.
    Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol 1998;16:137–61.PubMedCrossRefGoogle Scholar
  38. 38.
    Dotto GP. p21WAF1/Cip1: more than a break to the cell cycle? Biochem Biophys Acta 2000;1471:M43–56.PubMedGoogle Scholar
  39. 39.
    Pavletich NP. Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J Mol Biol 1999;287:821–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Meek DW. The p53 response to DNA damage. DNA Repair 2004;3:1049–56.PubMedCrossRefGoogle Scholar
  41. 41.
    Lu X. p53: a heavily dictated dictator of life and death. Curr Opin Genet Dev 2005;15:27–33.PubMedCrossRefGoogle Scholar
  42. 42.
    Dupont S, et al. Convergence of p53 and TGF-beta signaling networks. Cancer Lett 2004;213:129–38.PubMedCrossRefGoogle Scholar
  43. 43.
    Haupt S, Haupt Y. Manipulation of the tumor suppressor p53 for potentiating cancer therapy. Semin Cancer Biol 2004;14:244–52.PubMedCrossRefGoogle Scholar
  44. 44.
    May P, May E. Twenty years of p53 research: structural and functional aspects of the p53 protein. Oncogene 1999;18:7621–36.PubMedCrossRefGoogle Scholar
  45. 45.
    Heiser D, Labi V, Erlacher M, Villunger A. The Bcl-2 protein family and its role in the development of neoplastic disease. Exp Gerontol 2004;39:1125–35.PubMedCrossRefGoogle Scholar
  46. 46.
    Lozano G, Zambetti GP. What have animal models taught us about the p53 pathway? J Pathol 2005;205:206–20.PubMedCrossRefGoogle Scholar
  47. 47.
    Kuo P, Lin CC. Green tea constituent (-)-epigallocatechin-3-gallate inhibits Hep G2 cell proliferation and induces apoptosis through p53-dependent and Fas-mediated pathways. J Biomed Sci 2003;10:219–27.PubMedGoogle Scholar
  48. 48.
    Nihal M, Ahmad N, Mukhtar H, Wood GS. Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: possible implications for the chemoprevention of melanoma. Int J Cancer 2005;114:513–21.PubMedCrossRefGoogle Scholar
  49. 49.
    Yang CS, Hong J, Hou Z, Sang S. Green tea polyphenols: antioxidative and prooxidative effects. J Nutr 2004;134:3181S.PubMedGoogle Scholar
  50. 50.
    Szeto YT, Benzie IFF. Effects of dietary antioxidants on human DNA ex vivo. Free Radic Res 2002;36:113–8.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • S. Harakeh
    • 1
  • K. Abu-El-Ardat
    • 1
  • M. Diab-Assaf
    • 1
  • A. Niedzwiecki
    • 2
  • M. El-Sabban
    • 3
  • M. Rath
    • 2
  1. 1.Biology DepartmentAmerican University of BeirutBeirutLebanon
  2. 2.Dr. Rath Research InsituteSanta ClaraUSA
  3. 3.Human Morphology DepartmentAmerican University of BeirutBeirutLebanon

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