title: 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 72 h) 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 10 µg/mL of AgNPs for 7 days, or after discontinuous exposure by treating the cells every 3 days, for 15 or 30 days. Moreover, epigenetic changes in the acetylation of the histone H3 protein and in global DNA methylation patterns were determined after 72 h of exposure. Results showed that daily exposure to low doses of AgNPs, or a single exposure to high concentrations for 72 h, 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 72 h 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 72 h 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.
authors.affiliation: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorens 21, 43201, Reus, Catalonia, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Blanco
authors.affiliation: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorens 21, 43201, Reus, Catalonia, Spain.
authors.forename: Daisy
authors.initials: D
authors.lastname: Lafuente
authors.affiliation: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorens 21, 43201, Reus, Catalonia, Spain.|Biochemistry Unit, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorens 21, 43201, Reus, Catalonia, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Gómez
authors.affiliation: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorens 21, 43201, Reus, Catalonia, Spain.|Biochemistry Unit, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorens 21, 43201, Reus, Catalonia, Spain.
authors.forename: Tánia
authors.initials: T
authors.lastname: García
authors.affiliation: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorens 21, 43201, Reus, Catalonia, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Domingo
authors.affiliation: Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorens 21, 43201, Reus, Catalonia, Spain. domingo.sanchez@urv.cat.
authors.forename: Domènec J
authors.initials: DJ
authors.lastname: Sánchez
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D011205:Povidone / Q000737:chemistry*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D012834:Silver / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C468783:H2AX protein, human; D006657:Histones; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D012834:Silver; D013482:Superoxide Dismutase; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D053148:Caspase 3; D011205:Povidone
keywords: Cancer cells; Cytotoxicity; DNA methylation; Histone H3; Oxidative stress; Silver nanoparticles