9208 POSTER Activity of CKD-581, Histone Deacetylase Inhibitor, in Cutaneous T-cell Lymphoma Models

Abstract

pathophysiology of aging. In the recent years, PPAR-gamma, activated by J2 series cyclopentenol prostoglandin (cyPGs), was observed to have anti-proliferative, apoptotic, differentiation and anti-inflammatory effects on various cancer cells. The aim of this study is to investigate the cytotoxic and apoptotic effects of CAPE in CCRF-CEM cell line. Material and Methods: The cytotoxicity of CAPE evaluated by Trypan blue dye exclusion test and XTT methods and apoptosis was examined with Acridine orange/Ethidium Bromide dye, Cell death detection ELISA and JC-1 mitochondrial membrane potential assay kit. Results: CAPE had dose and time dependent cytotoxicity and had 10 mM IC50 in CCRF-CEM cell line. ELISA and Acridine Orange/Ethidium Bromide dye and JC-1 methods revealed that CAPE induced apoptosis in the cell line. The effect associated with PPAR-gamma and hemeoxygenase is evaluated with Western Blotting. According to the flow-cytometric analysis of JC-1 stain, cell viability is detected as 38.13% for control, 29.78% for 24 hour, 26.76% for 48 hour, 25.82% for 72 hour and 25.22% for 96 hour. It was detected that 10mM concentration caused an increase till 24 hour and in the following period it caused a reduction when the effect of CAPE on PPAR-gamma expression was analyzed. Conclusion: Since CAPE is a chemotherapeutic and anti-tumoral agent with very less toxic effects on normal tissues, these results opened a new horizon for use of CAPE in the treatment of acute lymphoblastic leukemia.