Abstract 3662: Melatonin inhibits cell proliferation and induces apoptosis in human acute leukemia T and lymphoma B cells via a receptor independent mechanism

Abstract

Abstract Loss of melatonin (MLT) production due to age contributes to immunosenescence onset and age-related diseases such as cancer. MLT reduces proliferation in many different cancer cell lines. However, MLT effects on subjects with immune cell cancer are controversial, and little is known about its action mechanisms in human malignant lymphoid cells. In the current study, we examined the effect of different doses of MLT (0.5, 1 and 2 mM) administration on human acute leukemia T cells (Jurkat), Burkitt (Ramos), diffuse large B cell lymphoma (Sudhl4) and follicular B no-Hodgkin lymphoma (Dohh2) cells analyzing cell cycle arrest, apoptosis, caspase cascade activation pathway and the role of melatonin transmembrane receptors. The data showed that high concentrations (millimolar) of melatonin significantly inhibited progression from G1 to S phase of the cell cycle and increased apoptotic cell death via caspase cascade activation and poly-ADP-ribose polymerase (PARP) and caspase-3 and −9 cleavages in all cell lines studied. There was also evidence of caspase-8 activation in Ramos and Sudhl4 cells. Reduced levels of procaspase-8 were detected in Dohh2 cells after melatonin treatment, thus evidence of activation even though the cleaved fragment was not detected. Interestingly, downregulation of Bcl-2 and Bcl-XL expression was also observed in melatonin treatment in Dohh2 cells whereas Mcl-1 antiapoptotic protein expression remained unchanged in each malignant cell line studied. A significant decrease in mitochondrial membrane potential (ΔΨm) was also detected in Ramos cells. Finally, using luzindole (LZD), as a MT1 and MT2 melatonin membrane receptor antagonist, we observed that MLT inhibited cell proliferation and apoptotic cell death by means of a melatonin membrane receptor independent pathway. This novel finding shows that a nontoxic natural indoleamine may be a potential therapy for some types of human lymphoid malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3662.