ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: role of oxidative stress

Nanomedicine. 2011 Dec;7(6):904-13. doi: 10.1016/j.nano.2011.04.011. Epub 2011 May 19.

Abstract

Zinc oxide (ZnO) nanoparticles (NPs) are increasingly recognized for their utility in biological applications, including biosensor and medicine. However, little is known about the toxicity mechanisms of ZnO nanorods in human cells. This study was designed to investigate the possible mechanisms of apoptosis induced by ZnO nanorods in human alveolar adenocarcinoma (A549) cells. ZnO nanorod was found to induce cytotoxicity, reactive oxygen species (ROS) generation, oxidative stress and activities of caspase-3 & caspase-9 in a dose- and time-dependent manner. Western blot results showed that ZnO nanorods induced the expression of heat shock protein 70, a first-tier marker of cell damage and a cell-cycle checkpoint protein p53. Moreover, pro-apoptotic protein bax was upregulated and the antiapoptotic proteins, survivin and bcl-2, were downregulated in ZnO nanorod exposed cells. In conclusion, our data demonstrates that ZnO nanorod induced apoptosis in A549 cells through ROS and oxidative stress via p53, survivin, bax/bcl-2 and caspase pathways.

From the clinical editor: This study describes the mechanisms of apoptosis induced by ZnO nanorods in human alveolar adenocarcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Bronchiolo-Alveolar / drug therapy*
  • Adenocarcinoma, Bronchiolo-Alveolar / metabolism
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Nanotubes / chemistry*
  • Nanotubes / ultrastructure
  • Oxidative Stress
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects
  • Survivin
  • Tumor Suppressor Protein p53 / metabolism*
  • Zinc Oxide / chemistry
  • Zinc Oxide / pharmacology*
  • bcl-2-Associated X Protein / metabolism

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Survivin
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Caspase 3
  • Caspase 9
  • Zinc Oxide