TiO2 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.
KeywordsTiO2 nanoparticles Cd pollution Co-exposure Human health hazard Oxidative stress Apoptosis
The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this work through research group no. RG- 1439-72.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Capaldo A, Gay F, Scudiero R, Trinchella F, Caputo I, Lepretti M, Marabotti A, Esposito C, Laforgia V (2016) Histological changes, apoptosis and metallothionein levels in triturus carnifex (amphibia, urodela) exposed to environmental cadmium concentrations. Aquat Toxicol 173:63–73CrossRefGoogle Scholar
- Cesmeli S, Avci CB (2018) Application of titanium dioxide (TiO2) nanoparticles in cancer therapies. J Drug Target 5:1–5Google Scholar
- Yang WW, Miao AJ, Yang LY (2012) Cd2+ toxicity to green alga Chlamydomonas reinhardtii as influenced by its adsorption of TiO2 engineered nanoparticles. PLoS One 7:1–8Google Scholar
- Zande M, Undas AK, Kramer E, Monopoli MP, Peters RJ, Garry D, Fernandes EA, Hendriksen PJ, Marvin HP, Peijnenburg AA, Bouwmeester H (2016) Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action. Nanotoxicology 10:1431–1441CrossRefGoogle Scholar