Differential effect of cerium nanoparticles on the viability, redox-status and Ca-signaling system of cancer cells of various origins.

The present study aims to understand the molecular mechanism underlying the therapeutic effect of cerium nanoparticles (CeNPs) in oncology. Cancer cells were treated with different concentrations of pure nanocerium of different sizes synthesized by laser ablation. Due to the not insignificant influence of surface defects and oxygen species on the ROS-modulating properties of cerium nanoparticles, the nanoparticles were not coated with surfactants or organic molecules during synthesis, which could potentially inhibit a number of pro-oxidative effects. Reactive oxygen species (ROS) production, expression of genes encoding redox-status proteins, selenoproteins and proteins regulating cell death and endoplasmic reticulum stress (ER-stress) were investigated as indicators of the molecular mechanism of cancer cell death. Studies were conducted on the effects of cerium nanoparticles on the Ca signaling system of cancer cells of different origins. Mouse fibroblasts (L-929 cell line) were used as non-cancerous ("normal") cells for which a whole series of experiments were performed, and a comparative analysis of the effects of nanoceria. It was found that 75 nm-sized cerium nanoparticles did not affect the redox-status and ROS production of cancer cells. In fibroblast cells, however, this nanoparticle diameter led to a deterioration of the cellular redox status and ROS production in a wide range of nanoparticle concentrations. Larger nanoparticles (100 nm-sized and 160 nm-sized), on the other hand, showed a different effect on cancer cells of different origins. In mouse fibroblast L-929 cells, however, 100 nm-sized or 160 nm-sized CeNPs acted in a high concentration range to disrupt mitochondrial membrane potential and activate early apoptosis. High concentrations of CeNPs were required to increase ROS production, reduce redox-status and induce apoptosis in human A-172 glioblastoma cells compared to the hepatocellular carcinoma cell line HepG2 and the breast cancer cell line MCF-7. In the A-172 glioblastoma cells, ER-stress was also not activated and their Ca signaling system was activated by a significantly higher concentration of CeNPs, which could also contribute to the formation of tolerance of this cancer cell line to nanoceria. The Ca signaling system of mouse fibroblasts was found to be highly sensitive to activation by nanoceria and the cells produced Ca2+ signals with higher amplitude compared to A-172 and MCF-7 cells.