Investigation the cytotoxicity effects of CuO nanoparticles in combination with ionizing radiation and hyperthermia on Chronic Myelogenous Leukemia (CML)

Introduction: Chronic Myelogenous Leukemia (CML) is a malignant. Although CML initially respond to cancer therapy but later develop resistance and drawback chemotherapy. Therefore, it is urgent to develop new effective anticancer drugs, with more cancer cell targeting. The present study Investigation the cytotoxicity effects of CuO nanoparticles in combination with ionizing radiation and hyperthermia on Chronic Myelogenous Leukemia (CML). Methods: The present study was carried out in two stages. In first the CuO NPs characterization with Transmission electron microscopy (TEM) and antiproliferative effects of 100 μg/ml CuO NPs, hyperthermia (41 0C for 1 h) and irradiation (200 cGy) was investigated. In second stage, 100 μg/ml CuO NPs respectively combined with hyperthermia (41 0C for 1 h) and irradiation (200 cGy) and antiproliferative effects was evaluation. Cytotoxicity assays includes MTT, Cell viability, ROS production and detection the levels of Caspase 3, 8 and 9. Also 800 nm Doxorubicin was used as the positive control group. P-values of less than 0.05 were considered statistically significantResults: Our results indicated that Treatment of CML with 100 µg/ml with R+H have a significant (p<0.01) decrease Cell viability (0.146±0.016), a significant (p<0.05) increase apoptosis percent (62±2.06) percent of CML and a significant (p<0.05) increase generation of ROS (33.00±1.26) in compared with control. Also, a significant increase (p<0.05) in the activity of caspase-3 (0.41±0.022) and caspase -9 (0.209±0.016) was observed but Caspase-8 activity was not significant (P=0.074) changed.Conclusion: These findings revealed that the multi-agent CuO NPs combined caused inhibition of growth with increased in generation of ROS, apoptotic death of Chronic Myelogenous Leukemia. Also present study showed multi-agent CuO NPs induced cell apoptosis through mitochondrial membrane potential with increase as well as caspase-3 and -9 activations that can be considered in future studies.

Keywords:

CuO Nanoparticles , Hyperthermia , irradiation , Chronic Myelogenous Leukemia