Strobilurin fungicide kresoxim-methyl effects on a cancerous neural cell line: oxidant/antioxidant responses and in vitro migration

Toxicol Mech Methods. 2018 Nov;28(9):709-716. doi: 10.1080/15376516.2018.1506848. Epub 2018 Sep 12.

Abstract

In this paper we report the effects of the complex III inhibitor, strobilurin fungicide kresoxim-methyl, on the cellular homeostasis of a mammalian cancerous neural cell line. We examined whether exposure to subcytotoxic concentrations of kresoxim-methyl induce cellular and biochemical mechanisms of toxicity on the murine neuroblastoma N2a cells. Results revealed elevation of mitochondrial superoxide generation, decrease in mitochondrial transmembrane potential, losses on GPx enzyme activity, along with increased nitrite release. Fungicide exposure also induced impaired cellular migration. Our findings suggest that kresoxim-methyl, besides targeting the mitochondria in fungi, exerts its mode of action in mammalian cancer cells. Abbreviations: CAT: catalase; DMEM: Dulbecco's modified Eagle's medium; GPx: glutathione peroxidase; KM: kresoxym-methyl; N2a: mouse neuroblastoma cells; NO: nitric oxide.

Keywords: Complex III inhibitor; fungicide; in vitro migration; neuroblastoma cells; strobilurins.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Fungicides, Industrial / toxicity*
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neurons / drug effects*
  • Neurons / enzymology
  • Neurons / metabolism
  • Oxidants / metabolism*
  • Strobilurins / toxicity*

Substances

  • Antioxidants
  • Fungicides, Industrial
  • Oxidants
  • Strobilurins
  • kresoxim-methyl