Knockdown of glutamate cysteine ligase catalytic subunit by siRNA causes the gold nanoparticles-induced cytotoxicity in lung cancer cells

PLoS One. 2015 Mar 19;10(3):e0118870. doi: 10.1371/journal.pone.0118870. eCollection 2015.

Abstract

Gold nanoparticles (GNPs) have shown promising medical applications in cancer treatment involved in the regulation of intracellular redox balance. Previously, we have reported that GNPs can trigger apoptosis and necrosis in human lung cancer cells (A549) when L-buthionine-sulfoximine (BSO) was used to decrease the expression of intracellular glutathione (GSH). Herein, we investigated the cytotoxicity of GNPs toward lung cancer cells under the glutamate cysteine ligase catalytic subunit (GCLC) was silenced by siRNA. Our results showed that GNPs cause apoptosis and necrosis in cells transfected with GCLC siRNA by elevating intracellular reactive oxygen species (ROS). These findings demonstrated that the regulation of glutathione synthesis by GCLC siRNA in A549 cells can initiate the gold nanoparticles-induced cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Catalytic Domain / genetics
  • Cell Line, Tumor
  • DNA Primers / genetics
  • Flow Cytometry
  • Gene Knockdown Techniques / methods*
  • Glutamate-Cysteine Ligase / genetics*
  • Gold / toxicity*
  • Humans
  • Lung Neoplasms / metabolism*
  • Metal Nanoparticles / toxicity*
  • RNA, Small Interfering / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA Primers
  • RNA, Small Interfering
  • Gold
  • Glutamate-Cysteine Ligase

Grants and funding

This work was supported by the National Natural Science Foundation of China (81102468 to Y. Zhao). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.