title: Iron oxide nanoparticles induce oxidative stress, DNA damage, and caspase activation in the human breast cancer cell line.
abstract: Broad applications of iron oxide nanoparticles require an improved understanding of their potential effects on human health. In the present study, we explored the underlying mechanism through which iron oxide nanoparticles induce toxicity in human breast cancer cells (MCF-7). MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) and lactate dehydrogenase assays were used to examine mechanisms of cytotoxicity. Concentration- and time-dependent cytotoxicity was observed in MCF-7 cells. Iron oxide nanoparticles were found to induce oxidative stress evidenced by the elevation of reactive oxygen species generation, lipid peroxidation, and depletion of superoxide dismutase, glutathione, and catalase activities in MCF-7 cells. Nuclear staining was performed using 4', 6-diamidino-2-phenylindole (DAPI), and cells were analyzed with a fluorescence microscope. Iron oxide nanoparticles (60 μg/ml) induced substantial apoptosis that was identified by morphology, condensation, and fragmentation of the nuclei of the MCF-7 cells. It was also observed that the iron oxide NPs induced caspase-3 activity. DNA strand breakage was detected by comet assay, and it occurred in a concentration- and time-dependent manner. Thus, the data indicate that iron oxide nanoparticles induced cytotoxicity and genotoxicity in MCF-7 cells via oxidative stress. This study warrants more careful assessment of iron oxide nanoparticles before their industrial applications.
authors.affiliation: Department of Zoology, College of Science, King Saud University, Box 2455, Riyadh, 11451, Saudi Arabia.
authors.forename: Saud
authors.initials: S
authors.lastname: Alarifi
authors.forename: Daoud
authors.initials: D
authors.lastname: Ali
authors.forename: Saad
authors.initials: S
authors.lastname: Alkahtani
authors.forename: M S
authors.initials: MS
authors.lastname: Alhader
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D005290:Ferric Compounds / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D061986:MCF-7 Cells; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D007211:Indoles; D017382:Reactive Oxygen Species; C000499:ferric oxide; C007293:DAPI; D053148:Caspase 3; D005978:Glutathione