Titanium Dioxide (TiO2) Nanoparticles Preferentially Induce Cell Death in Transformed Cells in a Bak/Bax-Independent Fashion

While the cytotoxic effects of titanium dioxide (TiO₂) nanoparticles have been under intense investigation, the molecular mechanisms of this cytotoxicity remain unknown. Here we investigated the influence of oncogenic transformation and a major apoptotic signaling pathway on cellular responses to TiO₂ nanoparticles. Isogenic wild-type (WT) and apoptosis-resistant (Bak^−/−Bax^−/−) cell lines with and without tumorigenic transformation were examined. TiO₂ nanoparticles preferentially reduced viability of tumorigenic cells in a dose-dependent fashion compared with their untransformed counterparts. Importantly, the elevated cytotoxicity of TiO₂ nanoparticles was independent of a major Bak/Bax-dependent apoptosis pathway. Because transformation does not affect cellular fluid-phase endocytosis or nanoparticle uptake, it is likely that the increased cytotoxicity in tumor cells is due to the interaction between TiO₂ nanoparticles and the lysosomal compartment. Overall, our data indicate that TiO₂ nanoparticles induce cytotoxicity preferentially in transformed cells independent of a major apoptotic signaling pathway.