title: Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles.
abstract: Autophagy has attracted a great deal of research interest in tumor therapy in recent years. An attempt was made in this direction and now we report that iron oxide NPs synthesized by us selectively induce autophagy in cancer cells (A549) and not in normal cells (IMR-90). It was also noteworthy that autophagy correlated with ROS production as well as mitochondrial damage. Protection of NAC against ROS clearly suggested the implication of ROS in hyper-activation of autophagy and cell death. Pre-treatment of cancer cells with 3-MA also exhibited protection against autophagy and promote cellular viability. Results also showed involvement of classical mTOR pathway in autophagy induction by iron oxide NPs in A549 cells. Our results had shown that bare iron oxide NPs are significantly cytotoxic to human cancer cells (A549) but not to the normal human lung fibroblast cells (IMR-90).In other words our nanoparticles selectively kill cancerous cells. It is encouraging to conclude that iron oxide NPs bear the potential of its applications in biomedicine, such as tumor therapy specifically by inducing autophagy mediated cell death of cancer cells.
authors.affiliation: Fibre Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India.
authors.forename: Mohd Imran
authors.initials: MI
authors.lastname: Khan
authors.forename: Akbar
authors.initials: A
authors.lastname: Mohammad
authors.forename: Govil
authors.initials: G
authors.lastname: Patil
authors.forename: S A H
authors.initials: SA
authors.lastname: Naqvi
authors.forename: L K S
authors.initials: LK
authors.lastname: Chauhan
authors.forename: Iqbal
authors.initials: I
authors.lastname: Ahmad
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D005290:Ferric Compounds / Q000737:chemistry*; D005453:Fluorescence; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018625:Microscopy, Atomic Force; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D017550:Spectroscopy, Fourier Transform Infrared; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D005290:Ferric Compounds; D017382:Reactive Oxygen Species; C000499:ferric oxide; D000255:Adenosine Triphosphate; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase