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


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.


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





Aryl hydrocarbon receptor


Human colorectal adenocarcinoma cell line


Chinese hamster ovary cell line


DNA methyltransferase 1


Estrogen receptor alpha


Estrogen receptor beta


Glyceraldehyde-3-phosphate dehydrogenase


Glucose transporter 2


Hexokinase 2


50% of inhibitory concentration


Insulin-like growth factor 1


Liver fatty acid-binding protein


Human breast adenocarcinoma cell line


Human breast epithelial cell line


O6-Methylguanine-DNA methyltransferase


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


Neutral red uptake


Peroxisome proliferator-activated receptor gamma


Pregnane X receptor


Human neuroblastoma cell line


Sterol regulatory element-binding protein 1



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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