Calcium titanate nanoparticlesinduced cytotoxicity, genotoxicity and oxidative stress in human nonsmall lung cancer cells

Abstract

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.