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Alterations in global DNA methylation and metabolism-related genes caused by zearalenone in MCF7 and MCF10F cells

  • Ecem Fatma Karaman
  • Sibel OzdenEmail author
Original Article
  • 41 Downloads

Abstract

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by Fusarium fungi. ZEN has endocrine disruptor effects and could impair the hormonal balance. Here, we aimed at investigating possible effects of ZEN on metabolism-related pathways and its relation to epigenetic mechanisms in breast adenocarcinoma (MCF7) and breast epithelial (MCF10F) cells. Using the MTT and neutral red uptake (NRU) cell viability tests, IC50 values of ZEN after 24 h were found to be 191 μmol/L and 92.6 μmol/L in MCF7 cells and 67.4 μmol/L and 79.5 μmol/L in MCF10F cells. A significant increase on global levels of 5-methylcytosine (5-mC%) was observed for MCF7 cells, correlating with the increased expression of DNA methyltransferases. No alterations were observed on levels of 5-mC% and expression of DNA methyltransferases for MCF10F cells. Further, at least threefold upregulation compared to control was observed for several genes related to nuclear receptors and metabolism in MCF7 cells, while some of these genes were downregulated in MCF10F cells. The most notably altered genes were IGF1, HK2, PXR, and PPARγ. We suggested that ZEN could alter levels of global DNA methylation and impair metabolism-related pathways.

Keywords

Zearalenone DNA methylation Metabolism-related genes Nuclear receptor genes MCF7 cells MCF10F cells 

Abbreviations

5-mC

5-Methylcytosine

AhR

Aryl hydrocarbon receptor

Caco-2

Human colorectal adenocarcinoma cell line

CHO-K1

Chinese hamster ovary cell line

DNMT1

DNA methyltransferase 1

ERα

Estrogen receptor alpha

ERβ

Estrogen receptor beta

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

GLUT2

Glucose transporter 2

HK2

Hexokinase 2

IC50

50% of inhibitory concentration

IGF1

Insulin-like growth factor 1

L-FABP

Liver fatty acid-binding protein

MCF7

Human breast adenocarcinoma cell line

MCF10F

Human breast epithelial cell line

MGMT

O6-Methylguanine-DNA methyltransferase

MTT

[3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide, a tetrazole]

NRU

Neutral red uptake

PPARɣ

Peroxisome proliferator-activated receptor gamma

PXR

Pregnane X receptor

SH-SY5Y

Human neuroblastoma cell line

SREBP1c

Sterol regulatory element-binding protein 1

Notes

Acknowledgements

This work was supported in part by the TUBITAK (2211-C/2015-2 grant for E.F.K.) and Scientific Research Projects Coordination Unit of Istanbul University (project no. TOA-2016-20307).

Compliance with ethical standards

Conflicts of interest

The authors report no conflicts of interest.

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Copyright information

© Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Toxicology, Faculty of PharmacyIstanbul UniversityIstanbulTurkey

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