Share This Article:

Green Tea Polyphenols Mediated Apoptosis in Intestinal Epithelial Cells by a Fadd-Dependent Pathway

Abstract Full-Text HTML XML Download Download as PDF (Size:854KB) PP. 105-113
DOI: 10.4236/jct.2010.13018    5,075 Downloads   9,831 Views   Citations

ABSTRACT

Colorectal cancer is the most common malignant complication in patients with chronic inflammatory bowel disease (IBD). In addition, these patients are at risk for developing painful complications during chemotherapy due to cytotoxic effects of drugs currently in use. Past studies have suggested a protective effect of tea consumption on gastrointestinal (GI) malignancies. Green tea polyphenols (GrTP) inhibited carcinogen-induced GI tumors in rodents and induced apoptosis in various carcinoma cell lines. We hypothesized that GrTP and its polyphenolic compounds regulate apoptosis in the intestinal epithelia. In this study, the effects of GrTP and its polyphenolics on apoptosis was evaluated in intestinal epithelial, IEC-6, cells grown to 85% confluency. GrTP (400-800 mg/ml) induced DNA fragmentation in a dose dependent fashion. Higher concentrations (> 800 mg/ml) induced a mixed apoptosis and cytolysis. Epithelial cells exposed to GrTP and a major polyphenol, EGCG, but not EGC or EC, increased caspase activities in a time and dose dependent manner. The caspase inhibitors rescued cells from GrTP and EGCG-induced cell death. Concomitantly, GrTP resulted in activation of fatty acid synthase (Fas)-associated protein with death domain (FADD) and recruitment to Fas/CD95 domain 30 minutes following treatment. While GrTP also blocked NF-?B activation, an NF-?B inhibitor (MG132) only promoted cytolysis. In conclusion, these data demonstrated GrTP and EGCG induced apoptosis in intestinal epithelia mediated by caspase-8 through a FADD dependent pathway. Future investigation may warrant preventive as well as therapeutic strategies for GrTP in GI malignancy.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

H. S. Oz and J. Ebersole, "Green Tea Polyphenols Mediated Apoptosis in Intestinal Epithelial Cells by a Fadd-Dependent Pathway," Journal of Cancer Therapy, Vol. 1 No. 3, 2010, pp. 105-113. doi: 10.4236/jct.2010.13018.

References

[1] W. Goessling and R. J. Mayer, “Systemic Treatment of Patients who Have Colorectal Cancer and Inflammatory Bowel Disease,” Gastroenterology Clinics of North America, Vol. 35, No. 3, 2006, pp. 713-727.
[2] J. Suchy, E. K?ujszo-Grabowska, J. K?adny, C. Cybulski, D. Woko?orczyk, J. Szymańska-Pasternak, G. Kurzawski, R. J. Scott and J. Lubiński, “Inflammatory Response Gene Polymorphisms and their Relationship with Colorectal Cancer Risk,” BMC Cancer, Vol. 23, No. 8, 2008, p. 112.
[3] J. H. Hendry and C. S. Potten, “Cryptogenic Cells and Proliferative Cells in Intestinal Epithelium,” International Journal of Radiation Biology & Related Studies in Physics, Chemistry & Medicine, Vol. 25, No. 4, 1974, pp. 583- 588.
[4] J. A. Hermos, M. Mathan and J. S. Trier, “DNA Synthesis and Proliferation by Villous Epithelial Cells in Fetal Rats,” Journal of Cell Biology, Vol. 50, No. 1, 1971, pp. 255- 258.
[5] H. S. Oz and J. L. Ebersole, “Application of Prodrugs to Inflammatory Diseases of the Gut,” Molecules, Vol. 13, No. 2, 2008, pp. 452-474.
[6] W. Strober, I. J. Fuss and R. S. Blumberg, “The Immu-nology of Mucosal Models of Inflammation,” Annual Re-view of Immunology, Vol. 20, No. 1, 2002, pp. 495-549.
[7] H. S. Oz, J. Zhong and W. de Villiers, “The Pattern Rec-ognition Scavenger Receptors, SR-A & CD36, Have Ad-ditive Roles in the Development of DSS-Induced Colitis in Mice,” Digestive Diseases Sciences, Vol. 54, No. 3, 2009, pp. 2247-2252.
[8] J. Doering, B. Begue, M. J. Lentze, F. Rieux-Laucat, O. Goulet, J. Schmitz, N. Cerf-Bensussan and F. M. Ruem-mele, “Induction of T Lymphocyte Apoptosis by Sulpha-salazine in Patients with Crohn’s Disease,” Gut, Vol. 53, No. 11, 2004, pp. 1632-1638.
[9] I. Mercier, M. Vuolo, J. F. Jasmin, C. M. Medina, M. Williams, J. M. Mariadason, H. Qian, X. Xue, R. G. Pes-tell, M. P. Lisanti and R. N. Kitsis, “ARC (Apoptosis Re-pressor with Caspase Recruitment Domain) is a Novel Marker of Human Colon Cancer,” Cell Cycle, Vol. 7, No. 11, 2008, pp. 1640-1647.
[10] H. Li, G. Ray, B. H. Yoo, M. Erdogan and K. V. Rosen, “Down-Regulation of Death-Associated Protein Kinase-2 is Required for Beta-Catenin-Induced Anoikis Resistance of Malignant Epithelial Cells,” Journal of Biological Chemistry, Vol. 284, No. 4, 2009, pp. 2012-2022.
[11] F. Yang, H. S. Oz, S. Barve, W. J. de Villiers, C. J. McClain and G. W. Varilek, “The Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate Blocks Nuclear Factor- Kappa B Activation by Inhibiting Ikappa B Kinase Activ-ity in the Intestinal Epithelial Cell Line IEC-6,” Molecular Pharmacology, Vol. 60, No. 3, 2001, pp. 528-533.
[12] H. S. Oz, C. J. McClain, H. T. Nagasaw, M. B. Ray, W. S. J. de Villiers and T. S. Chen, “Diverse Antioxidants Pro-tect against Acetaminophen Hepatotoxicity,” Journal of Biochemical and Molecular Toxicology, Vol. 18, No. 6, 2004, pp. 361-368.
[13] G. W. Varilek, F. Yang, E. Y. Lee, W. J. de Villiers, J. Zhong, H. S. Oz and C. J. McClain, “Green Tea Poly-phenol Extract Attenuates Inflammation in Interleukin- 2-Deficient Mice, a Model of Autoimmunity,” Journal of Nutrition, Vol. 131, No. 7, 2001, pp. 2034-2039.
[14] H. S. Oz, T. Chen, C. McClain and W. de Villiers, “An-tioxidants a Novel Therapy in a Murine Model of Colitis,” Journal of Nutritional Biochemistry, Vol. 16, No. 5, 2005, pp. 297-304.
[15] H. S. Oz and T. S. Chen, “Green-Tea Polyphenols Downregulate Cyclooxygenase and Bcl-2 Activity in Acetaminophen-Induced Hepatotoxicity,” Digestive Dis-eases Sciences, Vol. 53, No. 11, 2008, pp. 2980-2988.
[16] C. S. Yang, P. Maliakal and X. Meng, “Inhibition of Car-cinogenesis by Tea,” Annual Review of Pharmacology and Toxicology, Vol. 42, No. 1, 2002, pp. 25-54.
[17] T. Ohishi, Y. Kishimoto, N. Miura, G. Shiota, T. Kohri, Y. Hara, J. Hasegawa and M. Isemura, “Synergistic Effects of (-)-Epigallocatechin Gallate with Sulindac against Colon Carcinogenesis of Rats Treated with Azoxymethane,” Cancer Letters, Vol. 177, No. 1, 2002, pp. 49-56.
[18] Z. P. Chen, J. B. Schell, C. T. Ho and K. Y. Chen, “Green Tea Epigallocatechin Gallate Shows a Pronounced Growth Inhibitory Effect on Cancerous Cells but not on their Normal Counterparts,” Cancer Letters, Vol. 129, No. 2, 1998, pp. 173-179.
[19] M. Isemura, K. Saeki, T. Kimura, S. Hayakawa, T. Mi-nami and M. Sazuka, “Tea Catechins and Related Poly-phenols as Anti-Cancer Agents,” Biofactors, Vol. 13, No. 1-4, 2000, pp. 81-85.
[20] P. P. Wu, S. C. Kuo, W. W. Huang, J. S. Yang, K. C. Lai, H. J. Chen, K. L. Lin, Y. J. Chiu, L. J. Huang and J. G. Chung, “(-)-Epigallocatechin Gallate Induced Apoptosis in Human Adrenal Cancer NCI-H295 Cells through Cas-pase-Dependent and Caspase-Independent Pathway,” Anti-cancer Research, Vol. 29, No. 4, 2009, pp. 1435-1442.
[21] A. Basu and S. Haldar, “Combinatorial Effect of Epigal-locatechin-3-Gallate and TRAIL on Pancreatic Cancer Cell Death,” International Journal of Oncology, Vol. 34, No. 1, 2009, pp. 281-286.
[22] P. R. Twentyman and M. Luscombe, “A Study of Some Variables in a Tetrazolium Dye (MTT) Based Assay for Cell Growth and Chemosensitivity,” British Journal of Cancer, Vol. 56, No. 3, 1994, pp. 279-285.
[23] C. Fiocchi, “Inflammatory Bowel Disease: Etiology and Pathogenesis,” Gastroenterology, Vol. 115, No. 1, 1998, pp. 182-205.
[24] D. K. Podolsky, “Inflammatory Bowel Disease,” The New England Journal of Medicine, Vol. 347, No. 6, 2002, pp. 417-429.
[25] A. D. Levine, “Apoptosis: Implications for Inflammatory Bowel Disease,” Inflammatory Bowel Disease, Vol. 6, No. 3, 2000, pp. 191-205.
[26] D. Jourd'heuil, Z. Morise, E. M. Conner, J. Kurose and M. B. Grisham, “Oxidant-Regulation of Gene Expression in the Chronically Inflamed Intestine,” The Keio Journal of Medicine, Vol. 46, No. 1, 1997, pp. 10-15.
[27] J. Marks-Honczalik, S. C. Chu and J. Moss, “Cyto-kine-Mediated Transcriptional Induction of Human In-ducible Nitric Oxide Synthase Gene Requires both Acti-vator Protein-1 and Nuclear Factor κB Binding Sites,” Journal of Biological Chemistry, Vol. 273, No. 35, 1998, pp. 22201-22208.
[28] M. F. Neurath, C. Becker and K. Barbulescu, “Role of NF-Kappa B in Immune and Inflammatory Responses in the Gut,” Gut, Vol. 43, No. 6, 1998, pp. 856-860.
[29] J. Shibata, H. Goto, T. Arisawa, Y. Niwa, T. Hayakawa, A. Nakayama and N. Nori, “Regulation of Tumor Necrosis factor (TNF)-induced Apoptosis by Soluble TNF-Re- ceptors in Helicobacter pylori Infections,” Gut, Vol. 45, No. 1, 1999, pp. 24-31.
[30] M. J. Miller, F. M. Angeles, B. K. Reuter, P. Bobrowski and M. Sandoval, “Dietary Antioxidants Protect Gut Epi-thelial Cells from Oxidant-Induced Apoptosis,” BMC Complementary and Alternative Medicine, Vol. 1, No. 1, 2001, p. 11.
[31] S. Fiorucci, E. Antonelli, L. Santucci, O. Morelli, M. Miglietti, B. Federici, R. Mannucci, P. del Soldato and A. Morelli, “Gastrointestinal Safety of Nitric Oxide-Derived Aspirin is Related to Inhibition of ICE-Like Cysteine Proteases in Rats,” Gastroenterology, Vol. 116, No. 5, 1999, pp. 1089-1106.
[32] C. Jobin and R. B. Sartour, “The IκB/NF-κB System - A Key Determinant of Mucosal Inflammation and Protection,” American Journal of Physiology, Vol. 278, No. 3, 2000, pp. C451-C462.
[33] T. Zou, J. N. Rao, X. Guo, L. Liu, H. M. Zhang, E. D. Strauch, B. L. Bass and J. Y. Wang, “NF-KappaB-Me- diated IAP Expression Induces Resistance of Intestinal Epithelial Cells to Apoptosis after Polyamine Depletion,” American Journal of Physiology and Cell Physiology, Vol. 286, No. 5, 2004, pp. C1009-C1018.
[34] R. Atreya and M. F. Neurath, “New Therapeutic Strate-gies for Treatment of Inflammatory Bowel Disease,” Mucosal Immunology, Vol. 1, No. 3, 2008, pp. 175-182.
[35] D. Shim, H. Y. Kang, B. W. Jeon, S. S. Kang, S. I. Chang, H. Y. Kim, “Protein Kinase B Inhibits Apoptosis Induced by Actinomycin D in ECV304 Cells through Phosphory-lation of Caspase 8,” Archives of Biochemistry and Bi-ophysics, Vol. 425, No. 2, 2004, pp. 214-220.
[36] J. Searle, T. A. Lawson, P. J. Abbott, B. Harmon, J. F. Kerr, “An Electron-Microscope Study of the Mode of Cell Death Induced by Cancer-Chemotherapeutic Agents in Populations of Proliferating Normal and Neoplastic Cells,” Journal of Pathology, Vol. 116, No. 3, 1975, pp. 129-138.
[37] H. S. Oz, T. Chen and M. Neuman, “Methionine Defi-ciency and Liver Injury in a Dietary NASH Model,” Di-gestive Diseases Sciences, Vol. 53, No. 3, 2008, pp. 767-776.
[38] H. S. Oz, H. Im, T. Chen, W. de Villiers and C. McClain, “Glutathione Enhancing Agents Protect against Steatohe-patitis in a Model,” Journal of Biochemical and Molecular Toxicology, Vol. 20, No. 1, 2006, pp. 39-47.
[39] M. Neuman, “Immune Dysfunction in Inflammatory Bo-wel Disease,” Trans-Research, Vol. 149, No. 4, 2007, pp. 173-186.
[40] H. S. Oz, M. Ray, T. Chen and C. McClain, “Efficacy of a TGF-β2 Containing Nutritional Support Formula in a Murine Model of IBD,” Journal of American College of Nutrition, Vol. 23, No. 3, 2004, pp. 220-226.
[41] L. M. Gaetke, H. S. Oz, R. Frederich and C. McClain, “Anti-TNF-α Antibody Normalizes Serum Leptin in IL-2 Deficient Mice,” Journal of American College of Nutrition, Vol. 22, No. 5, 2003, pp. 415-420.
[42] K. Wright, G. Kolios, J. Westwick and S. G. Ward, “Cy-tokine-Induced Apoptosis in Epithelial HT-29 Cells is Independent of Nitric Oxide Formation,” Journal of Bio-logical Chemistry, Vol. 274, No. 24, 1999, pp. 17193- 17201.
[43] Q. Chang and B. L. Tepperman, “The Role of Protein Kinase C Isozymes in TNF-Alpha-Induced Cytotoxicity to a Rat Intestinal Epithelial Cell Line,” American Journal of Physiology Gastrointest Liver Physiology, Vol. 280, No. 4, 2001, pp. G572-G583.
[44] G. S. Salvesen and V. M. Dixit, “Caspases: Intracellular Signaling by Proteolysis,” Cell, Vol. 91, No. 4, 1997, pp. 443-446.
[45] M. Krajewska, H. G. Wang, S. Krajewski, J. M. Zapata, A. Shabaik, R. Gascoyne and J. C. Reed, “Immunohisto-chemical Analysis of in Vivo Patterns of Expression of CPP32 (Caspase-3), a Cell Death Protease,” Cancer Re-search, Vol. 57, No. 8, 1997, pp. 1605-1613.
[46] S. Gupta, K. Hastak, F. Afaq, N. Ahmad and H. Mukhtar, “Essential Role of Caspases in Epigallocatechin-3-Ga- llate-Mediated Inhibition of Nuclear Factor KappaB and Induction of Apoptosis,” Oncogene, Vol. 23, No. 14, 2004, pp. 2507-2516.
[47] J. Li, C. Y. Huang, R. L. Zheng, K. R. Cui and J. F. Li, “Hydrogen Peroxide Induces Apoptosis in Human Hepa-toma Cells and Alters Cell Redox Status,” Cell Biology International, Vol. 24, No. 1, 2000, pp. 9-23.
[48] M. Nihal, H. Ahsan, I. A. Siddiqui, H. Mukhtar, N. Ah-mad and G. S. Wood, “(-)-Epigallocatechin-3-Gallate (EGCG) Sensitizes Melanoma Cells to Interferon Induced Growth Inhibition in a Mouse Model of Human Melano-ma,” Cell Cycle, Vol. 8, No. 13, 2009, pp. 2057-2063.
[49] T. Bohler, J. Waiser, H. Hepburn, J. Gaedeke, C. Lehmann, P. Hambach, K. Budde and H. H. Neumayer, “TNF-Alpha and IL-1 Alpha Induce Apoptosis in Subconfluent Rat Mesangial Cells. Evidence for the Involvement of Hydrogen Peroxide and Lipid Peroxidation as Second Messengers,” Cytokine, Vol. 12, No. 7, 2000, pp. 986-991.
[50] K. Kahlos, Y. Soini, P. Paako, M. Saily, K. Linnainmaa, V. L. Kinnula, “Proliferation, Apoptosis, and Manganese Superoxide Dismutase in Malignant Mesothelioma,” In-ternational Journal of Cancer, Vol. 88, No. 11, 2000, pp. 37-43.
[51] M. H. Pan, C. C. Lin, J. K. Lin and W. J. Chen, “Tea Polyphenol (-)-Epigallocatechin 3-Gallate Suppresses Heregulin-Beta1-Induced Fatty Acid Synthase Expression in Human Breast Cancer Cells by Inhibiting Phosphatidy-linositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase Cascade Signaling,” Journal of Agricultural and Food Chemistry, Vol. 55, No. 13, 2007, pp. 5030-5037.
[52] S. Hsu, J. Lewis, B. Singh, P. Schoenlein, T. Osaki, M. Athar, A. G. Porter and G. Schuster, “Green Tea Poly-phenol Targets the Mitochondria in Tumor Cells Inducing Caspase 3-Dependent Apoptosis,” Anticancer Research, Vol. 23, No. 2B, 2003, pp. 1533-1539.
[53] B. S. Mantej, R. Borojevic, S. Basak, E. Ho, P. Zhou and K. Croitoru, “IL-10 Protects Mouse Intestinal Epithelial Cells from Fas-Induced Apoptosis via Modulating Fas Expression and Altering Caspase-8 and FLIP Expression,” American Journal of Physiology Gastrointest Liver Phy-siology, Vol. 291, No. 5, 2006, pp. G820-G829.
[54] R. W. Johnstone, A. A. Ruefli and S. W. Lowe, “Apopto-sis: A Link Review between Cancer Genetics and Che-motherapy,” Cell, Vol. 108, No. 2, 2002, pp. 153-164.
[55] F. Vandermeers, P. Hubert, P. Delvenne, C. Mascaux, B. Grigoriu, A. Burny, A. Scherpereel and L. Willems, “Val- proate, in Combination with Pemetrexed and Cisplatin, Provides Additional Efficacy to the Treatment of Malignant Mesothelioma,” Clinical Cancer Research, Vol. 15, No. 8, 2009, pp. 2818-2828.
[56] H. H. Chow, Y. Cai, I. A. Hakim, J. A. Crowell, F. Shahi, C. A. Brooks, R. T. Dorr, Y. Hara and D. S. Alberts, “Pharmacokinetics and Safety of Green Tea Polyphenols after Multiple-Dose Administration of Epigallocatechin Gallate and Polyphenon E in Healthy Individuals,” Clinical Cancer Research, Vol. 9, No. 9, 2003, pp. 3312- 3319.

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.