Imatinib Mesylate induces apoptosis in chronic myeloid leukemia cells by triggering nitric oxide production

Aim: Chronic Myeloid Leukemia (CML) is a myeloproliferative disease characterized by abnormal clonal proliferation of hematopoietic stem cells. The overproduction of nitric oxide (NO) causes reactive oxygen species and subsequent oxidative stress to cell toxicity. The production of factors such as nitric oxide (NO) and reactive oxygen species (ROS) in the cell and/or tissue environment affects the behavior of normal cells and cancer cells. In this study, we aimed to investigate the effects of nitric oxide formed as a result of Imatinib Mesylate (STI571, Gleevec (R)) metabolism on cell death. Material and Methods: 32D (Control) and 32DP210 Cells were treated with 10um of Imatinib Mesylate for 24, 48 and 72 hours. Methyl tetrazolium assay (MTT) was used for cell viability. Griess assay and capillary electrophoresis were used to measure Imatinib Mesylate-mediated NO production. The number of cells leading to apoptosis was calculated by counting 1000 cells and compared with the amount of NO. Statistical analysis of the obtained data was done with SPSS for Windows statistical package program. Results: The presence of NO is important for increased cell death in the cell culture medium. Imatinib mesylate concentrations administered to healthy and CML groups increased intra cell NO levels by a significant amount in Bcr-Abl+ CML cell lines. The production of NO per apoptotic body is decreased during the apoptosis, and analysis of NO production using CE in these cells has rapid and efficient separation ability. Discussion: As a result, knowing the molecules and effects regulating NO activity better appears to be a target point to remove many irregularities of these molecules. Sensitive detection of these metabolic products is important as variations in NO levels in many diseases provide information about development of diseases and treatment.