Cell type-specific activation of AKT and ERK signaling pathways by small negatively-charged magnetic nanoparticles

Sci Rep. 2012;2:868. doi: 10.1038/srep00868. Epub 2012 Nov 16.

Abstract

The interaction of nanoparticles (NPs) with living organisms has become a focus of public and scientific debate due to their potential wide applications in biomedicine, but also because of unwanted side effects. Here, we show that superparamagnetic iron oxide NPs (SPIONs) with different surface coatings can differentially affect signal transduction pathways. Using isogenic pairs of breast and colon derived cell lines we found that the stimulation of ERK and AKT signaling pathways by SPIONs is selectively dependent on the cell type and SPION type. In general, cells with Ras mutations respond better than their non-mutant counterparts. Small negatively charged SPIONs (snSPIONs) activated ERK to a similar extent as epidermal growth factor (EGF), and used the same upstream signaling components including activation of the EGF receptor. Importantly, snSPIONs stimulated the proliferation of Ras transformed breast epithelial cells as efficiently as EGF suggesting that NPs can mimic physiological growth factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • ErbB Receptors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Ferric Compounds / chemistry
  • HCT116 Cells
  • Humans
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / toxicity
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects

Substances

  • Ferric Compounds
  • Magnetite Nanoparticles
  • Protein Kinase Inhibitors
  • ferric oxide
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases