Silver nanoparticles induce apoptosis and G2/M arrest via PKCζ-dependent signaling in A549 lung cells
- 711 Downloads
The use of silver nanoparticles is one of the fastest growing product categories in the nanotechnology industry, with a focus on antimicrobial activity. However, thus far, toxicity data for silver nanoparticles are limited. In this study, we investigated the cytotoxic effects of silver nanoparticles (Ag NPs) and the pathway by which they affect A549 lung epithelial cells. The effects of Ag NPs on cell survival, cell cycle progression, and mRNA and protein alterations of selected cell cycle- and apoptosis-related genes were studied using formazan dye and LDH release assays, flow cytometric analysis, semi-quantitative RT-PCR, and Western blot analysis. Ag NPs reduced cell viability, increased LDH release, and modulated cell cycle distribution through the accumulation of cells at G2/M and sub-G1 phases (cell death), with a concurrent decrease in cells at G1. Ag NP treatment increased Bax and Bid mRNA levels and downregulated Bcl-2 and Bcl-w mRNAs in a dose-dependent manner. Furthermore, Ag NPs altered the mRNA levels of protein kinase C (PKC) family members. In particular, ectopic overexpression of PKCζ led to the enhancement of cellular proliferation and reduced sensitivity to Ag NPs in A549 cells. Together, these results suggest that Ag NPs induce strong toxicity and G2/M cell cycle arrest by a mechanism involving PKCζ downregulation in A549 cells.
KeywordsSilver nanoparticles (Ag NPs) G2/M arrest Apoptosis Protein kinase C (PKC) ζ
This work was supported by a 2009 General Project grant from the Ministry of Knowledge and Economy through the International Inhalation Toxicology Evaluation Technology program at the Korea Institute of Toxicology.
- Cioffi N, Ditaranto N, Torsi L, Picca RA, De Giglio E, Sabbatini L, Novello L, Tantillo G, Bleve-Zacheo T, Zambonin PG (2005) Synthesis, analytical characterization and bioactivity of Ag and Cu nanoparticles embedded in poly-vinyl-methyl-ketone films. Anal Bioanal Chem 382:1912–1918PubMedCrossRefGoogle Scholar
- Cohen A, Brodie C, Sarid R (2006) An essential role of ERK signalling in TPA-induced reactivation of Kaposi’s sarcoma-associated herpesvirus. J Gen Virol 87:795–802Google Scholar
- Kutsuzawa K, Chowdhury EH, Nagaoka M, Maruyama K, Akiyama Y, Akaike T (2006) Surface functionalization of inorganic nano-crystals with fibronectin and E-cadherin chimera synergistically accelerates trans-gene delivery into embryonic stem cells. Biochem Biophs Res Commun 350:514–520CrossRefGoogle Scholar
- Kvitek L, Soukupova J (2009) Comment on ‘Preparation and antibacterial activity of Fe3O4@ Ag nanoparticles’. Nanotechnology 20:028001Google Scholar
- Lee HY, Park HK, Lee YM, Kim K, Park SB (2007) A practical procedure for producing silver nanocoated fabric and its antibacterial evaluation for biomedical applications. Chem Commun 28:2959–2961Google Scholar
- Morita Y, Naka T, Kawazoe Y, Fujimoto M, Nakagawa R, Fukuyama H, Nagata S, Kishimoto T (2000) Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis factor α-induced cell death in fibroblasts. Proc Natl Acad Sci USA 91:5405–5410Google Scholar