Titanium Dioxide Induces Apoptosis under UVA Irradiation via the Generation of Lysosomal Membrane Permeabilization-Dependent Reactive Oxygen Species in HaCat Cells

Titanium dioxide nanoparticles (TiO2 NPs) have wide commercial applications, owing to their small size; however, the biosafety of TiO2 NPs should be evaluated further. In this study, we aimed to investigate the cytotoxicity of TiO2 NPs in the presence and absence of ultraviolet A (UVA) irradiation in human keratinocyte HaCaT cells. TiO2 NPs did not significantly affect cell viability in the absence of UVA irradiation. Nonetheless, UVA-irradiated TiO2 NPs induced caspase-dependent apoptosis of HaCaT cells. Exposure of HaCaT cells to TiO2 NPs and UVA resulted in reactive oxygen species (ROS) generation and lysosomal membrane permeabilization (LMP); both effects were not observed in the absence of UVA irradiation. An analysis of the relationship between LMP and ROS, using CA-074 as a cathepsin inhibitor or NAC as an antioxidant, showed that LMP stimulates ROS generation under these conditions. These results imply that LMP-dependent oxidative stress plays a critical role in the UVA phototoxicity of TiO2 NPs in HaCaT cells.