Titanium dioxide (TiO2) nanoparticles preferentially induce cell death in transformed cells in a Bak/Bax-independent fashion.

While the cytotoxic effects of titanium dioxide (TiO(2)) 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 TiO(2) nanoparticles. Isogenic wild-type (WT) and apoptosis-resistant (Bak(-/-)Bax(-/-)) cell lines with and without tumorigenic transformation were examined. TiO(2) nanoparticles preferentially reduced viability of tumorigenic cells in a dose-dependent fashion compared with their untransformed counterparts. Importantly, the elevated cytotoxicity of TiO(2) 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 TiO(2) nanoparticles and the lysosomal compartment. Overall, our data indicate that TiO(2) nanoparticles induce cytotoxicity preferentially in transformed cells independent of a major apoptotic signaling pathway.