title: Silver nanoparticles-induced cytotoxicity requires ERK activation in human bladder carcinoma cells.
abstract: Silver nanoparticles are toxic both in vitro and in vivo. We have investigated the possibility to exploit the cytotoxic potential of silver nanoparticles in T24 bladder carcinoma cells using both bare and PolyVinylPyrrolidone-coated silver nanoparticles. We show that the two types of silver nanoparticles promote morphological changes and cytoskeletal disorganization, are cytotoxic and induce cell death. These effects are due to the increased production of reactive oxygen species which are responsible, at least in part, for the sustained activation of ERK1/2. Indeed, both cytotoxicity and ERK1/2 activation are prevented by exposing the cells to the anti-oxidant N-acetylcysteine. Also blocking the ERK1/2 pathway with the MEK inhibitor PD98059 protects the cells from nanoparticles' cytotoxicity. Our findings suggest that ERK activation plays a role in silver nanoparticle-mediated cytotoxicity in T24 cells.
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, Milano I-20157, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Castiglioni
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, Milano I-20157, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cazzaniga
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, Milano I-20157, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Perrotta
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, Milano I-20157, Italy. Electronic address: jeanette.maier@unimi.it.
authors.forename: Jeanette A M
authors.initials: JA
authors.lastname: Maier
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000737:chemistry / Q000633:toxicity*; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D017382:Reactive Oxygen Species; D012834:Silver; D048052:Mitogen-Activated Protein Kinase 3; D000111:Acetylcysteine
keywords: Bladder cancer cell; Cytotoxicity; ERK; Reactive oxygen species; Silver nanoparticles