title: Cobalt iron oxide nanoparticles induce cytotoxicity and regulate the apoptotic genes through ROS in human liver cells (HepG2).
abstract: Cobalt iron oxide (CoFe2O4) nanoparticles (CIO NPs) have been one of the most widely explored magnetic NPs because of their excellent chemical stability, mechanical hardness and heat generating potential. However, there is limited information concerning the interaction of CIO NPs with biological systems. In this study, we investigated the reactive oxygen species (ROS) mediated cytotoxicity and apoptotic response of CIO NPs in human liver cells (HepG2). Diameter of crystalline CIO NPs was found to be 23nm with a band gap of 1.97eV. CIO NPs induced cell viability reduction and membrane damage, and degree of induction was dose- and time-dependent. CIO NPs were also found to induce oxidative stress revealed by induction of ROS, depletion of glutathione and lower activity of superoxide dismutase enzyme. Real-time PCR data has shown that mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were higher, while the expression level of anti-apoptotic gene bcl-2 was lower in cells following exposure to CIO NPs. Activity of caspase-3 and caspase-9 enzymes was also higher in CIO NPs exposed cells. Furthermore, co-exposure of N-acetyl-cysteine (ROS scavenger) efficiently abrogated the modulation of apoptotic genes along with the prevention of cytotoxicity caused by CIO NPs. Overall, we observed that CIO NPs induced cytotoxicity and apoptosis in HepG2 cells through ROS via p53 pathway. This study suggests that toxicity mechanisms of CIO NPs should be further investigated in animal models.
authors.affiliation: King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, 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, Saudi Arabia.
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: M A Majeed
authors.initials: MAM
authors.lastname: Khan
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; Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
authors.forename: Aws
authors.initials: A
authors.lastname: Alshamsan
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D053148:Caspase 3 / Q000235:genetics; D053453:Caspase 9 / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003035:Cobalt / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013052:Spectrometry, X-Ray Emission; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014961:X-Ray Diffraction; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494826:BAX protein, human; D005290:Ferric Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C569492:cobalt ferrite; D003035:Cobalt; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptosis; Biomedical applications; Cobalt iron oxide (CoFe(2)O(4)); Cytotoxicity; ROS