TiO 2 particles induce ER stress and apoptosis in human hepatoma cells, HepG2, in a particle size-dependent manner

The cytotoxicity of TiO nanoparticles are well-known, but the particle size-dependent induction of ER stress and apoptosis by TiO in hepatocytes has not been elucidated clearly. In the present study, we investigated whether a fine TiO particle and two types of TiO nanoparticles induce ER stress and apoptosis differently in HepG2 cells. A particle size-dependent decrease in cell viability was observed after exposure to the TiO particles. The levels of ER stress-related proteins (BiP, CHOP, ATF6α, and p-PERK) were increased with decreasing particle size. TiO particles induced ER stress-mediated apoptosis in a particle size-dependent manner as seen by a decrease in the expression of Bcl-2, and increases in the expression of Bax, caspase-12, and cleaved caspase-3. These results indicated that the cytotoxicity produced by TiO particles was related to particle size, with smaller TiO nanoparticles producing greater toxic effects involving ER stress and apoptosis in the HepG2 cells.