Silver nanoparticles regulate autophagy through lysosome injury and cell hypoxia in prostate cancer cells

J Biochem Mol Toxicol. 2020 May;34(5):e22474. doi: 10.1002/jbt.22474. Epub 2020 Feb 11.

Abstract

With the rapid development of nanotechnology, nanomaterials are now being used for cancer treatment. Although studies on the application of silver nanoparticles in cancer treatment are burgeoning, few studies have investigated the toxicology mechanisms of autophagy in cancer cells under exposure to sublethal silver nanoparticles. Here, we clarified the distinct mechanisms of silver nanoparticles for the regulation of autophagy in prostate cancer PC-3 cells under sublethal exposure. Silver nanoparticle treatment caused lysosome injury, including the decline of lysosomal membrane integrity, decrease of lysosomal quantity, and attenuation of lysosomal protease activity, which resulted in blockage of autophagic flux. In addition, sublethal silver nanoparticle exposure activated AMP-activated protein kinase/mammalian target of rapamycin-dependent signaling pathway to modulate autophagy, which resulted from silver nanoparticles-induced cell hypoxia and energy deficiency. Taken together, the results show that silver nanoparticles could regulate autophagy via lysosome injury and cell hypoxia in PC-3 cells under sublethal dose exposure. This study will provide an experimental basis for the cancer therapy of nanomaterials.

Keywords: autophagy; cancer cell; hypoxia; lysosome; silver nanoparticles.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Apoptosis / drug effects
  • Autophagy / drug effects*
  • Autophagy / genetics
  • Cell Hypoxia / drug effects*
  • Cell Hypoxia / genetics
  • Cell Survival / drug effects
  • Drug Delivery Systems / methods
  • Gene Knockdown Techniques
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Lysosomes / drug effects*
  • Male
  • Metal Nanoparticles / administration & dosage*
  • PC-3 Cells
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Silver / administration & dosage
  • Silver / pharmacology*
  • TOR Serine-Threonine Kinases / metabolism
  • Transfection

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Silver
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases