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

Widespread application of titanium dioxide nanoparticles (nTiO2) and ubiquitous cadmium (Cd) pollution may increase their chance of co-existence in the natural environment. Toxicological information on co-exposure of nTiO2 and Cd in mammalian models is largely lacking. Hence, we studied the combined effects of nTiO2 and Cd in human liver (HepG2) and breast cancer (MCF-7) cells. We observed that nTiO2 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 nTiO2 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, nTiO2 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 nTiO2 facilitates the internalization of Cd into the cells. Overall, this study demonstrated that non-cytotoxic concentration of nTiO2 enhanced the toxicological potential of Cd in human cells. Therefore, more attention should be paid on the combine effects of nTiO2 and Cd on human health.