title: Silver nanoparticles induce toxicity in A549 cells via ROS-dependent and ROS-independent pathways.
abstract: Silver nanoparticles (AgNPs) are incorporated into a large number of consumer and medical products. Several experiments have demonstrated that AgNPs can be toxic to the vital organs of humans and especially to the lung. The present study evaluated the in vitro mechanisms of AgNP (<100 nm) toxicity in relationship to the generation of reactive oxygen species (ROS) in A549 cells. AgNPs caused ROS formation in the cells, a reduction in their cell viability and mitochondrial membrane potential (MMP), an increase in the proportion of cells in the sub-G1 (apoptosis) population, S phase arrest and down-regulation of the cell cycle associated proliferating cell nuclear antigen (PCNA) protein, in a concentration- and time-dependent manner. Pretreatment of the A549 cells with N-acetyl-cysteine (NAC), an antioxidant, decreased the effects of AgNPs on the reduced cell viability, change in the MMP and proportion of cells in the sub-G1population, but had no effect on the AgNP-mediated S phase arrest or down-regulation of PCNA. These observations allow us to propose that the in vitro toxic effects of AgNPs on A549 cells are mediated via both ROS-dependent (cytotoxicity) and ROS-independent (cell cycle arrest) pathways.
authors.affiliation: Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Rd, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Porntipa
authors.initials: P
authors.lastname: Chairuangkitti
authors.forename: Somsong
authors.initials: S
authors.lastname: Lawanprasert
authors.forename: Sittiruk
authors.initials: S
authors.lastname: Roytrakul
authors.forename: Sasitorn
authors.initials: S
authors.lastname: Aueviriyavit
authors.forename: Duangkamol
authors.initials: D
authors.lastname: Phummiratch
authors.forename: Kornphimol
authors.initials: K
authors.lastname: Kulthong
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
authors.forename: Rawiwan
authors.initials: R
authors.lastname: Maniratanachote
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000633:toxicity*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; D012834:Silver