Silica nanoparticles and lead acetate co-exposure triggered synergistic cytotoxicity in A549 cells through potentiation of mitochondria-dependent apoptosis induction

Environ Toxicol Pharmacol. 2017 Jun;52:114-120. doi: 10.1016/j.etap.2017.04.001. Epub 2017 Apr 3.


The adverse effects of PM2.5 are the results of combined toxicities of finer particles and their adsorbed toxic pollutants. Nevertheless, the combined toxicity of finer particles and air pollutants still remains unclear. The present study was therefore undertaken to investigate the combined cytotoxicity of silica nanoparticles (nano-SiO2, a typical atmospheric ultrafine particle) and lead acetate (Pb, a representative air pollutant) in A549 cells focusing on mitochondria-dependent apoptosis induction. The results showed that Pb exposure alone induced mitochondria-dependent apoptosis in A549 cells, as evidenced by increased apoptotic rate and Bax/Bcl-2 ratio, up-regulated caspases 3 and 9 expressions as well as decreased mitochondrial membrane potential. Non-cytotoxic concentration of nano-SiO2 exposure alone did not trigger apoptosis in A549 cells, but potentialized the apoptotic changes when co-exposure with Pb. Factorial analyses revealed synergistic interactions were responsible for the potentiation of joint apoptotic responses.

Keywords: Apoptosis; Combined toxicity; Lead; PM2.5; Silica nanoparticles; Synergism.

MeSH terms

  • A549 Cells
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Survival / drug effects
  • Drug Synergism
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • Nanoparticles / toxicity*
  • Organometallic Compounds / toxicity*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Silicon Dioxide / toxicity*


  • Organometallic Compounds
  • Proto-Oncogene Proteins c-bcl-2
  • Silicon Dioxide
  • Caspase 3
  • Caspase 9
  • lead acetate