Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles

Biomaterials. 2012 Feb;33(5):1477-88. doi: 10.1016/j.biomaterials.2011.10.080. Epub 2011 Nov 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adenylate Kinase / metabolism
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology*
  • Ferric Compounds / chemistry*
  • Fluorescence
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology*
  • Membrane Potential, Mitochondrial / drug effects
  • Microscopy, Atomic Force
  • Mitochondria / drug effects
  • Mitochondria / pathology*
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Nanoparticles / ultrastructure
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Spectroscopy, Fourier Transform Infrared
  • TOR Serine-Threonine Kinases / metabolism
  • X-Ray Diffraction

Substances

  • Ferric Compounds
  • Reactive Oxygen Species
  • ferric oxide
  • Adenosine Triphosphate
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Adenylate Kinase