CuO nanoparticles induce cytotoxicity and apoptosis in human K۵۶۲ cancer cell line via mitochondrial pathway, through reactive oxygen species and P۵۳

Objective(s): This study focused on determining cytotoxic effects of copper oxide nanoparticles (CuO NPs) on chronic myeloid leukemia (CML) K۵۶۲ cell line in a cell-specific manner and its possible mechanism of cell death. We investigated the cytotoxicity of CuO NPs against K۵۶۲ cell line (cancerous cell) and peripheral blood mononuclear cell (normal cell). Materials and Methods: The toxicity was evaluated using cell viability, oxidative stress and apoptosis detection. In addition, the expression levels of P۵۳, Caspase ۳, Bcl-۲, and Bax genes in K۵۶۲ cells were studied by reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: CuO NPs exerted distinct effects on cell viability via selective killing of cancer cells in a dose-dependent manner while not impacting normal cells in MTT assay. The dose-dependent cytotoxicity of CuO NPs against K۵۶۲ cells was shown through reactive oxygen species (ROS) generation. The CuO NPs induced apoptosis was confirmed through acridine orange and propidium iodide double staining. Tumor suppressor gene P۵۳ was up regulated due to CuO NPs exposure, and increase in Bax/Bcl-۲ ratio suggested mitochondria-mediated pathway is involved in CuO NPs induced apoptosis. We also observed that Caspase ۳ gene expression remained unchanged up to ۲۴ hr exposure.                                                                             Conclusion: These molecular alterations provide an insight into CuO NPs-caused inhibition of growth, generation of ROS, and apoptotic death of K۵۶۲ cells.

Keywords:

Apoptosis , Bax/Bcl-۲ , CuO nanoparticles , K۵۶۲ , P۵۳ , ROS , Cancer