Abstract A28: The effects of combined treatment with NF-κB inhibitors and arsenic trioxide on leukemic cell lines

Abstract

Abstract Arsenic trioxide (ATO) induces growth inhibition and apoptosis in a wide variety of cancer cell lines. Some reports indicate that this effect can be enhanced by inhibiting the activity of transcription factor NF-κB. The aim of our study was to evaluate the efficacy of combined treatment with ATO and selected NF-κB inhibitors (sulindac, parthenolide, BAY 11-7082, MG-132 and gliotoxin) in inducing cell death of five leukemic cell lines: EL-4 mouse thymoma, Jurkat, HL-60, K562 and HPB-ALL. The cytotoxicity of the chemicals was evaluated using 72-hrs WST-1 reduction assay and apoptosis was assessed with Annexin V-FITC/propidium iodide staining (FACS). We observed that among the inhibitors tested, gliotoxin and MG-132 when used alone showed the highest cytotoxicity on all cell lines (effective concentrations less than 1 μM). Parthenolide and BAY11-7082 induced complete death of all cell lines at the concentration of 10 μM. All four inhibitors did not potentiated the effects of ATO used at 0.5 or 1 μM. Although sulindac was the least cytotoxic compound when used alone, it showed the highest potentiating effect on ATO induced cytotoxicity on all cell lines. The response of cells to the combination was rather diverse with Jurkat and HPB-ALL cells being the most sensitive. As a rule, all cell lines treated simultaneously with ATO (1 μM) and sulindac (100 μM) showed complete decrease in viability after 72 hrs. The results with annexin V/PI staining indicated apoptosis as the main cell death mechanism. This combination had much weaker effect on the viability of healthy blood lymphocytes. The results of our study reveal an interesting cytotoxic effect of ATO with combination with sulindac on a panel of leukemic cell lines. The work was supported by the Polish State Committee for Scientific Research (grant No PB 2806/B/PO1/2007/33). Citation Information: Clin Cancer Res 2010;16(7 Suppl):A28