title: Nanotoxicity of cobalt induced by oxidant generation and glutathione depletion in MCF-7 cells.
abstract: There are very few studies regarding the biological activity of cobalt-based nanoparticles (NPs) and, therefore, the possible mechanism behind the biological response of cobalt NPs has not been fully explored. The present study was designed to explore the potential mechanisms of the cytotoxicity of cobalt NPs in human breast cancer (MCF-7) cells. The shape and size of cobalt NPs were characterized by scanning and transmission electron microscopy (SEM and TEM). The crystallinity of NPs was determined by X-ray diffraction (XRD). The dissolution of NPs was measured in phosphate-buffered saline (PBS) and culture media by atomic absorption spectroscopy (AAS). Cytotoxicity parameters, such as [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT), neutral red uptake (NRU), and lactate dehydrogenase (LDH) release suggested that cobalt NPs were toxic to MCF-7 cells in a dose-dependent manner (50-200μg/ml). Cobalt NPs also significantly induced reactive oxygen species (ROS) generation, lipid peroxidation (LPO), mitochondrial outer membrane potential loss (MOMP), and activity of caspase-3 enzymes in MCF-7 cells. Moreover, cobalt NPs decreased intracellular antioxidant glutathione (GSH) molecules. The exogenous supply of antioxidant N-acetyl cysteine in cobalt NP-treated cells restored the cellular GSH level and prevented cytotoxicity that was also confirmed by microscopy. Similarly, the addition of buthionine-[S, R]-sulfoximine, which interferes with GSH biosynthesis, potentiated cobalt NP-mediated toxicity. Our data suggested that low solubility cobalt NPs could exert toxicity in MCF-7 cells mainly through cobalt NP dissolution to Co2+.
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia. Electronic address: mohd.j.akhtar@gmail.com.
authors.forename: Mohd Javed
authors.initials: MJ
authors.lastname: Akhtar
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Maqusood
authors.initials: M
authors.lastname: Ahamed
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia; Department of Physics and Astronomy, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Hisham A
authors.initials: HA
authors.lastname: Alhadlaq
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia; Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Aws
authors.initials: A
authors.lastname: Alshamsan
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry / Q000633:toxicity*; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D003035:Cobalt; D019328:Buthionine Sulfoximine; D053148:Caspase 3; D005978:Glutathione; D000111:Acetylcysteine
keywords: Cobalt nanoparticles; GSH; Lipid peroxidation; NPs dissolution; ROS