Calcium titanate nanoparticles-induced cytotoxicity, genotoxicity and oxidative stress in human non-small lung cancer cells

Calcium titanate nanoparticles (CaTiO₃NPs) have garnered significant attention due to their unique properties and excellent biocompatibility, which have led to their increased use in various fields and consumer products. This rise in application necessitates a better understanding of their biological and toxicological effects. However, there is limited data on the cytotoxicity and genotoxicity of CaTiO₃NPs in human normal skin fibroblasts (HSF) and non-small lung cancer (A-549) cells. Consequently, this study aimed to explore the effect of 48-hour exposure to CaTiO₃NPs on cell viability, genomic DNA integrity, and oxidative stress induction in human cancer A-549 cells, compared to normal HSF cells. The cytotoxicity and genotoxicity of CaTiO₃NPs were assessed using the Sulforhodamine B (SRB) cytotoxicity and Alkaline Comet assays, respectively. To estimate possible oxidative stress induction and variation in apoptotic gene expression, reactive oxygen species (ROS) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were also performed. Our findings demonstrated that exposure to CaTiO₃NPs for 48 h resulted in low toxicity toward both normal HSF and cancer A-549 cells, with cell death observed only at high concentrations (100 and 1000 µg/ml). The IC50 value of CaTiO₃NPs in both HSF and A-549 cells was greater than 1000 µg/ml; specifically, the IC50 value in A-549 cells at 48 h was 1670.65 µg /ml. However, treatment with CaTiO₃NPs for 48 h at the IC50 concentration of 1670.65 µg /ml resulted in significant genomic DNA damage and excessive ROS generation, along with a notable disturbance in the expression level of apoptotic (p53 and Bax) and anti-apoptotic Bcl2 genes in A-549 cells. In contrast, no significant changes were observed in HSF cells treated for 48 h with the same concentration (1670.65 µg /ml) of CaTiO₃NPs. Collectively, these findings indicated that despite short-term exposure to CaTiO₃NPs causing low cytotoxicity in both normal HSF and A-549 cells. CaTiO₃NPs were selectively genotoxic toward A-549 cells. This genotoxicity was mediated through excessive ROS generation, which disrupted genomic DNA integrity and altered the expression of apoptotic genes, triggering apoptosis in A-549 cells. Further in vitro and in vivo studies are needed to fully understand the toxicological and biological properties of CaTiO₃NPs.