Silver-doped graphene oxide nanocomposite triggers cytotoxicity and apoptosis in human hepatic normal and carcinoma cells

Int J Nanomedicine. 2018 Sep 24:13:5685-5699. doi: 10.2147/IJN.S165448. eCollection 2018.

Abstract

Introduction: Graphene oxide nanoparticles have been widely used in industry and biomedical fields due to their unique physicochemical properties. However, comparative cytotoxicity of silver-doped reduced graphene oxide (rGO-Ag) nanoparticles on normal and cancerous liver cells has not been well studied yet.

Materials and methods: This study aimed at determining the toxic potential of rGO-Ag nanocomposite on human liver normal (CHANG) and cancer (HepG2) cells. The rGO-Ag nanocomposite was characterized by using different advanced instruments, namely, dynamic light scattering, scanning electron microscope, and transmission electron microscope.

Results: The rGO-Ag nanocomposite reduced cell viability and impaired cell membrane integrity of CHANG and HepG2 cells in a dose-dependent manner. Additionally, it induced reactive oxygen species generation and reduced mitochondrial membrane potential in both cells in a dose-dependent manner. Moreover, the activity of oxidative enzymes such as lipid peroxide, superoxide dismutase, and catalase were increased and glutathione was reduced in both cells exposed to rGO-Ag nanocomposite. Pretreatment with N-acetylcysteine inhibited cytotoxicity and reactive oxygen species generation in CHANG and HepG2 cells exposed to rGO-Ag nanocomposite (50 µg/mL). DNA damage was determined by Comet assay and maximum DNA damage occurred at rGO-Ag nanocomposite (25 µg/mL) for 24 h. It is also valuable to inform that HepG2 cells appear to be slightly more susceptible to rGO-Ag nanocomposite exposure than CHANG cells.

Conclusion: This result provides a basic comparative toxic effect of rGO-Ag nanocomposite on hepatic normal and cancerous liver cells.

Keywords: CHANG and HepG2 cells; DNA fragmentation; apoptosis; cytotoxicity; oxidative stress.

MeSH terms

  • Acetylcysteine / pharmacology
  • Apoptosis* / drug effects
  • Catalase / metabolism
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • DNA Damage
  • Glutathione / metabolism
  • Graphite / chemistry*
  • Hep G2 Cells
  • Humans
  • Lipid Peroxides / metabolism
  • Liver / pathology*
  • Liver Neoplasms / pathology*
  • Membrane Potential, Mitochondrial / drug effects
  • Metal Nanoparticles / chemistry
  • Nanocomposites / chemistry*
  • Nanocomposites / ultrastructure
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Silver / chemistry*
  • Superoxide Dismutase / metabolism

Substances

  • Lipid Peroxides
  • RNA, Messenger
  • Reactive Oxygen Species
  • graphene oxide
  • Silver
  • Graphite
  • Catalase
  • Superoxide Dismutase
  • Glutathione
  • Acetylcysteine