title: CuO nanoparticles induce cytotoxicity and apoptosis in human K562 cancer cell line via mitochondrial pathway, through reactive oxygen species and P53.
abstract: OBJECTIVE
  This study focused on determining cytotoxic effects of copper oxide nanoparticles (CuO NPs) on chronic myeloid leukemia (CML) K562 cell line in a cell-specific manner and its possible mechanism of cell death. We investigated the cytotoxicity of CuO NPs against K562 cell line (cancerous cell) and peripheral blood mononuclear cell (normal cell).
  
  
  METHODS
  The toxicity was evaluated using cell viability, oxidative stress and apoptosis detection. In addition, the expression levels of P53, Caspase 3, Bcl-2, and Bax genes in K562 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 K562 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 P53 was up regulated due to CuO NPs exposure, and increase in Bax/Bcl-2 ratio suggested mitochondria-mediated pathway is involved in CuO NPs induced apoptosis. We also observed that Caspase 3 gene expression remained unchanged up to 24 hr exposure.
  
  
  CONCLUSIONS
  These molecular alterations provide an insight into CuO NPs-caused inhibition of growth, generation of ROS, and apoptotic death of K562 cells.
authors.affiliation: Department of Biology and Institute of Biotechnology, Faculty of Sciences, Urmia University, Urmia, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shafagh
authors.affiliation: Department of Biology and Institute of Biotechnology, Faculty of Sciences, Urmia University, Urmia, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Rahmani
authors.affiliation: Microbiology Department, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
authors.forename: Norouz
authors.initials: N
authors.lastname: Delirezh
keywords: Apoptosis; Bax/Bcl-2; CuO NPs; K562; P53; ROS