Cytotoxicity of NiO and Ni(OH)2 Nanoparticles Is Mediated by Oxidative Stress-Induced Cell Death and Suppression of Cell Proliferation

Int J Mol Sci. 2020 Mar 28;21(7):2355. doi: 10.3390/ijms21072355.

Abstract

The use of nanomaterial-based products continues to grow with advancing technology. Understanding the potential toxicity of nanoparticles (NPs) is important to ensure that products containing them do not impose harmful effects to human or environmental health. In this study, we evaluated the comparative cytotoxicity between nickel oxide (NiO) and nickel hydroxide (Ni(OH)2) in human bronchoalveolar carcinoma (A549) and human hepatocellular carcinoma (HepG2) cell lines. Cellular viability studies revealed cell line-specific cytotoxicity in which nickel NPs were toxic to A549 cells but relatively nontoxic to HepG2 cells. Time-, concentration-, and particle-specific cytotoxicity was observed in A549 cells. NP-induced oxidative stress triggered dissipation of mitochondrial membrane potential and induction of caspase-3 enzyme activity. The subsequent apoptotic events led to reduction in cell number. In addition to cell death, suppression of cell proliferation played an essential role in regulating cell number. Collectively, the observed cell viability is a function of cell death and suppression of proliferation. Physical and chemical properties of NPs such as total surface area and metal dissolution are in agreement with the observed differential cytotoxicity. Understanding the properties of NPs is essential in informing the design of safer materials.

Keywords: apoptosis; caspase-3; cell cycle; cell proliferation; mitochondrial membrane potential; nanoparticles; oxidative stress; physicochemical properties; viability.

MeSH terms

  • A549 Cells
  • Cell Death / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Hep G2 Cells
  • Humans
  • Hydroxides / toxicity*
  • Nanoparticles / toxicity*
  • Nickel / toxicity*
  • Oxidative Stress / drug effects

Substances

  • Hydroxides
  • nickel hydroxide
  • Nickel
  • nickel monoxide