TiO 2 nanoparticles potentiated the cytotoxicity, oxidative stress and apoptosis response of cadmium in two different human cells

Widespread application of titanium dioxide nanoparticles (nTiO 2 ) and ubiquitous cadmium (Cd) pollution may increase their chance of co-existence in the natural environment. Toxicological information on co-exposure of nTiO 2 and Cd in mammalian models is largely lacking. Hence, we studied the combined effects of nTiO 2 and Cd in human liver (HepG2) and breast cancer (MCF-7) cells. We observed that nTiO 2 did not produce toxicity to HepG2 and MCF-7 cells. However, moderate concentration of Cd exposure caused cytotoxicity to both cells. Interestingly, non-cytotoxic concentration of nTiO 2 effectively enhanced the oxidative stress response of Cd indicated by pro-oxidants generation (reactive oxygen species, hydrogen peroxide, and lipid peroxidation) and antioxidants depletion (glutathione level and glutathione reductase, superoxide dismutase, and catalase enzymes). Moreover, nTiO 2 potentiated the Cd-induced apoptosis in both cells suggested by altered expression of p53, bax, and bcl-2 genes along with low mitochondrial membrane potential. Cellular uptake results demonstrated that nTiO 2 facilitates the internalization of Cd into the cells. Overall, this study demonstrated that non-cytotoxic concentration of nTiO 2 enhanced the toxicological potential of Cd in human cells. Therefore, more attention should be paid on the combine effects of nTiO 2 and Cd on human health.