Archives of Toxicology

, Volume 85, Issue 12, pp 1529–1540 | Cite as

Silver nanoparticles induce apoptosis and G2/M arrest via PKCζ-dependent signaling in A549 lung cells

  • Young Sook Lee
  • Dong Woon Kim
  • Young Ho Lee
  • Jung Hwa Oh
  • Seokjoo Yoon
  • Mi Sun Choi
  • Sung Kyu Lee
  • Ji Won Kim
  • Kyuhong Lee
  • Chang-Woo Song
Inorganic Compounds

Abstract

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.

Keywords

Silver nanoparticles (Ag NPs) G2/M arrest Apoptosis Protein kinase C (PKC) ζ 

Notes

Acknowledgments

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.

Supplementary material

204_2011_714_MOESM1_ESM.tif (216 kb)
Supplementary material 1 (TIFF 216 kb)
204_2011_714_MOESM2_ESM.tif (202 kb)
Supplementary material 2 (TIFF 202 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Young Sook Lee
    • 1
  • Dong Woon Kim
    • 1
  • Young Ho Lee
    • 1
  • Jung Hwa Oh
    • 2
  • Seokjoo Yoon
    • 2
  • Mi Sun Choi
    • 2
  • Sung Kyu Lee
    • 3
  • Ji Won Kim
    • 3
  • Kyuhong Lee
    • 4
  • Chang-Woo Song
    • 4
  1. 1.Department of AnatomyChungnam National UniversityDaejeonRepublic of Korea
  2. 2.Molecular Toxicology TeamKorea Institute of ToxicologyDaejeonRepublic of Korea
  3. 3.Environmental Toxicology TeamKorea Institute of ToxicologyDaejeonRepublic of Korea
  4. 4.Department of Inhalation ToxicologyKorea Institute of Toxicology, Korea Research Institute of Chemical TechnologyJeongeupRepublic of Korea

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