title: Comparative cytotoxic response of nickel ferrite nanoparticles in human liver HepG2 and breast MFC-7 cancer cells.
abstract: Nickel ferrite nanoparticles (NPs) have received much attention for their potential applications in biomedical fields such as magnetic resonance imaging, drug delivery and cancer hyperthermia. However, little is known about the toxicity of nickel ferrite NPs at the cellular and molecular levels. In this study, we investigated the cytotoxic responses of nickel ferrite NPs in two different types of human cells (i.e., liver HepG2 and breast MCF-7). Nickel ferrite NPs induced dose-dependent cytotoxicity in both types of cells, which was demonstrated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT), neutral red uptake (NRU) and lactate dehydrogenase (LDH) assays. Nickel ferrite NPs were also found to induce oxidative stress, which was evident by the depletion of glutathione and the induction of reactive oxygen species (ROS) and lipid peroxidation. The mitochondrial membrane potential due to nickel ferrite NP exposure was also observed. The mRNA levels for the tumor suppressor gene p53 and the apoptotic genes bax, CASP3 and CASP9 were up-regulated, while the anti-apoptotic gene bcl-2 was down-regulated following nickel ferrite NP exposure. Furthermore, the activities of apoptotic enzymes (caspase-3 and caspase-9) were also higher in both types of cells treated with nickel ferrite NPs. Cytotoxicity induced by nickel ferrite was efficiently prevented by N-acetyl cysteine (ROS scavenger) treatment, which suggested that oxidative stress might be one of the possible mechanisms of nickel ferrite NP toxicity. We also observed that MCF-7 cells were slightly more susceptible to nickel ferrite NP exposure than HepG2 cells. This study warrants further investigation to explore the potential mechanisms of different cytotoxic responses of nickel ferrite NPs in different cell lines.
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: maqusood@gmal.com.
authors.forename: Maqusood
authors.initials: M
authors.lastname: Ahamed
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Mohd Javed
authors.initials: MJ
authors.lastname: Akhtar
authors.affiliation: Department of Physics and Astronomy, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Hisham A
authors.initials: HA
authors.lastname: Alhadlaq
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: M A Majeed
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Salman A
authors.initials: SA
authors.lastname: Alrokayan
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial; D053768:Metal Nanoparticles / Q000633:toxicity*; D009499:Neutral Red / Q000378:metabolism; D009532:Nickel / Q000633:toxicity*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D017382:Reactive Oxygen Species; C550717:nickel ferrite; D009499:Neutral Red; D009532:Nickel; D053148:Caspase 3; D053453:Caspase 9; D005978:Glutathione
keywords: Cytotoxicity; Human breast cells; Human health; Human liver cells; Nickel ferrite nanoparticles; Oxidative stress