Mycotoxin Alternariol (AOH) Affects Viability and Motility of Mammary Breast Epithelial Cells

Int J Mol Sci. 2021 Jan 12;22(2):696. doi: 10.3390/ijms22020696.

Abstract

Mycotoxins are present in everyday diet as common food and feed pollutants. A part of them is still concerned as so-called emerging mycotoxins. Due to the lack of toxicity data, the safety limits and detail molecular mechanism have been not established yet for all of them. Alternariol (AOH), as one of these mycotoxins, produced by Alternaria species, is so far reported as an estrogenic, genotoxic, and immunomodulatory agent; however, its direct effect on human health is not known. Especially, in the case of hormone-dependent tissues which are sensitive to both endogenic, as well as external estrogenic agents, it might be crucial to assess the effect of AOH. Thus, this study evaluated how exposure to AOH affects viability and motility of the human normal mammary gland epithelial in vitro model. We observed that AOH significantly affects viability of cells in a time- and dose-dependent manner. Moreover, the induction of oxidative stress, DNA damage, and cell cycle arrest in the G2/M cell cycle phase was observed. The motility of 184A1 cells was also significantly affected. On the molecular level, AOH induced antioxidative stress response via activation of Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway agents, as well as decrease in the phosphorylation of protein kinase B (Akt) and p44/42 (ERK 1-2) molecules, indicating that AOH might affect crucial signaling pathways in both physiological and pathophysiological processes in breast tissue.

Keywords: alternariol; mammary gland; motility; mycotoxins; oxidative stress.

MeSH terms

  • Alternaria / metabolism
  • Breast / drug effects*
  • Breast / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Division / drug effects
  • Cell Line
  • Cell Movement / drug effects*
  • Cell Survival / drug effects*
  • DNA Damage / drug effects
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • G2 Phase / drug effects
  • Humans
  • Lactones / pharmacology*
  • Mammary Glands, Human / drug effects*
  • Mammary Glands, Human / metabolism
  • Mycotoxins / pharmacology*
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects

Substances

  • Lactones
  • Mycotoxins
  • NF-E2-Related Factor 2
  • alternariol