Titanium dioxide nanoparticles induce apoptosis by interfering with EGFR signaling in human breast cancer cells

Environ Res. 2019 Aug;175:117-123. doi: 10.1016/j.envres.2019.05.001. Epub 2019 May 7.


Titanium dioxide nanoparticles, due to their smaller size and increased surface area comparted to the bulk form, are known to be bioreactive and have unexpected toxicological outcomes. Previous studies have shown that nanoscale titanium dioxide induces reactive oxygen species (ROS)-mediated cytotoxicity and genotoxicity. Although many reports have discussed the ROS-mediated cytotoxic effects of titanium dioxide nanoparticles (TiO2-NPs), their effects on the receptor-ligand association are unknown. In this study, the possibility that TiO2-NPs can interfere with the receptor-ligand binding was assessed by monitoring alterations in the phosphorylation status of proteins downstream of the epidermal growth factor receptor (EGFR) signaling cascade. TiO2-NPs blocked ligand-induced EGFR autophosphorylation, leading to the deactivation of EGFR downstream effectors such as Akt and extracellular signal-regulated kinase signaling, inducing cell death.

Keywords: Cytotoxicity; EGFR; Ligand-receptor interaction; Titanium dioxide nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis* / drug effects
  • Breast Neoplasms
  • Cell Line, Tumor
  • ErbB Receptors / metabolism
  • Humans
  • Metal Nanoparticles* / toxicity
  • Reactive Oxygen Species / metabolism
  • Signal Transduction* / drug effects
  • Titanium* / toxicity


  • Reactive Oxygen Species
  • titanium dioxide
  • Titanium
  • EGFR protein, human
  • ErbB Receptors