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

Karolina Kowalska,Marta Justyna Kozieł,Kamila Domińska,Agnieszka Wanda Piastowska-Ciesielska,Kinga Anna Urbanek,Dominika Ewa Habrowska-Górczyńska

doi:10.3390/ijms22020696

Karolina Kowalska, Marta Justyna Kozieł + Show 4 more

Open Access

https://doi.org/10.3390/ijms22020696

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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.

Highlights

Contrary to most of the endothelial cells, the mAmmary gland develops postnatal and includes complex epithelial remodeling in response to steroid hormones and growth factors.The steroid hormones mAinly responsible for mAmmary gland remodeling are estrogens and progesterone [1]
An induction of oxidative stress in cells is reported to be a cause of the exposure to mycotoxins [19]; we evaluated if decreased viability of 184A1 cells is associated with production of reactive oxygen species (ROS) in cells
Alternariol (AOH) from Alternaria sp., estrogen (E2), dimethyl sulfoxide (DMSO), 40,6-diamidine-20 -phenylindole dihydrochloride (DAPI), RIPA buffer, phenylmethylsulfonyl fluoride (PMSF), protease and phosphatase inhibitors, paraformaldehyde (PFA), acetic acid, methanol, ethanol, crystal violet, Triton X-100, and Coomassie brilliant blue were derived from Sigma Aldrich

Summary

Introduction

Contrary to most of the endothelial cells, the mAmmary gland develops postnatal and includes complex epithelial remodeling in response to steroid hormones and growth factors.The steroid hormones mAinly responsible for mAmmary gland remodeling are estrogens and progesterone [1]. A specific group of both natural, as well as synthetic, substances present in every day food and feed mAy interfere with the hormonal system and affects both hormonal balance, as well as hormone-dependent tissues, directly These “endocrine disruptors” (EDC), which mimic natural estrogens, are a group of more than 450 compounds [2] which significantly affects hormonal balance in humans and constitutes a global health problem [3]. Estrogens, both endogenous and xenoestrogens, as well as phytoestrogens, play an important role both in the development of breast epithelium by stimulating proliferation and ductal morphogenesis, as well as breast carcinogenesis [4]. The effect of a naturally-occurring EDC in food on human health is not fully elucidated

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