Green tea polyphenol (-)-epigallocatechin-3-gallate causes growth inhibition, induction of apoptosis and cell cycle arrest in cutaneous T-cell lymphoma cell lines

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Non-Hodgkin lymphoma is the sixth most common cancer in males and the fifth most common cancer in females in the United States with an estimated 56,390 new cases and 19,200 deaths in 2005. Chemoprevention via naturally occurring non-toxic agents could be a useful strategy for the management of lymphoma. Cutaneous T-cell lymphoma (CTCL) is a group of lymphoproliferative disorders characterized by localization of malignant T lymphocytes to the skin at presentation. In this study, we evaluated the anti-proliferative potential of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant found in green tea, against CTCL-derived cell lines representing different stages of disease progression. Employing CTCL-derived lines MJ, HH, SeAx, MyLA and human T cell lymphoblast-like cell line Jurkat. We determined the growth inhibitory and pro-apoptotic properties of EGCG. Our data demonstrated that a low concentration of EGCG (5 μM; for 48 hours) resulted in a significant inhibition of the growth and viability (up to 50%) of all the cell lines, albeit at different levels. EGCG treatment to the cutaneous lymphoma cells also resulted in a significant inhibition of the protein level of Ki-67, a marker of cellular proliferation marker. Further, as evident from the flow cytometric determination of cells labeled with the cationic dye 5,5’,6,6’-tetrachloro-1,1’,3,3’-tetraethylbenzimidazolylcarbocyanine iodide (JC-1), EGCG was found to result in a significant (up to 44%) loss of mitochondrial membrane potential in the cell lines studied, indicating an induction of apoptosis. This was further confirmed by a flow cytometric determination of Annexin V binding. Furthermore, as evident from DNA cell cycle analysis (BrdU incorporation), EGCG (5 μM; for 48 and 96 hours) treatment to the cells was found to result in significant cell cycle arrest, albeit at different stages and different rates in different cell lines. Based on this study, we suggest that EGCG could be developed as a chemopreventive agent or as an adjuvant therapy for the management of cutaneous lymphoma. However, detailed mechanistic in vitro and in vivo studies are needed to further evaluate the anti-lymphoma efficacy of EGCG in appropriate culture and animal models.