Polyvinyl pyrrolidone-coated silver nanoparticles in a human lung cancer cells: time- and dose-dependent influence over p53 and caspase-3 protein expression and epigenetic effects.

Abstract

The present study was aimed at providing a better understanding of the influence of silver nanoparticles (AgNPs) on the p53 tumor suppressor protein. Cell line A549 was exposed to a range of concentrations of AgNPs, and a time course (up to 72h) of cell viability was determined. We also determined the time course of gene and protein expression of p53, p21, murine double minute 2 (MDM2) and caspase-3. The expression of all of these proteins was also determined after daily exposure of the cells to 10µg/mL of AgNPs for 7days, or after discontinuous exposure by treating the cells every 3days, for 15 or 30days. Moreover, epigenetic changes in the acetylation of the histone H3 protein and in global DNA methylation patterns were determined after 72h of exposure. Results showed that daily exposure to low doses of AgNPs, or a single exposure to high concentrations for 72h, decreased gene and protein expression of p53, p21, MDM2 and caspase-3 in A549 cells. In contrast, a discontinuous exposure to low doses or a single exposure to low concentrations for 72h increased the levels of the active forms of p53 and caspase-3, as well as the p21 and MDM2 protein levels. In addition, exposure to high concentrations of AgNPs for 72h induced higher levels of global DNA methylation and global histone H3 deacetylation in A549 cells. These results provide new information on the toxic action of AgNPs.