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

Kim, Hyungjoo, Jeon, Donghwan, Oh, Sunhwa, Nam, KeeSoo, Son, Seogho, Chan Gye, Myung, Shin, Incheol
Environmental research 2019 v.175 pp. 117-123
apoptosis, breast neoplasms, cytotoxicity, epidermal growth factor receptors, genotoxicity, ligands, mitogen-activated protein kinase, monitoring, nanoparticles, neoplasm cells, protein phosphorylation, reactive oxygen species, surface area, titanium dioxide
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.