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Article

Deciphering the Molecular Mechanisms Sustaining the Estrogenic Activity of the Two Major Dietary Compounds Zearalenone and Apigenin in ER-Positive Breast Cancer Cell Lines

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Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail)-UMR_S1085, F-35000 Rennes, France
2
Laboratoire Nutrinov, Technopole Atalante Champeaux, 8 rue Jules Maillard de la Gournerie, 35012 Rennes CEDEX, France
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(2), 237; https://doi.org/10.3390/nu11020237
Received: 12 November 2018 / Revised: 14 January 2019 / Accepted: 14 January 2019 / Published: 22 January 2019
(This article belongs to the Special Issue Phytochemicals in Health and Disease)
The flavone apigenin and the mycotoxin zearalenone are two major compounds found in the human diet which bind estrogen receptors (ERs), and therefore influence ER activity. However, the underlying mechanisms are not well known. To unravel the molecular mechanisms that could explain the differential effect of zearalenone and apigenin on ER-positive breast cancer cell proliferation, gene-reporter assays, chromatin immunoprecipitation (ChIP) experiments, proliferation assays and transcriptomic analysis were performed. We found that zearalenone and apigenin transactivated ERs and promoted the expression of estradiol (E2)-responsive genes. However, zearalenone clearly enhanced cellular proliferation, while apigenin appeared to be antiestrogenic in the presence of E2 in both ER-positive breast cancer cell lines, MCF-7 and T47D. The transcriptomic analysis showed that both compounds regulate gene expression in the same way, but with differences in intensity. Two major sets of genes were identified; one set was linked to the cell cycle and the other set was linked to stress response and growth arrest. Our results show that the transcription dynamics in gene regulation induced by apigenin were somehow different with zearalenone and E2 and may explain the differential effect of these compounds on the phenotype of the breast cancer cell. Together, our results confirmed the potential health benefit effect of apigenin, while zearalenone appeared to be a true endocrine-disrupting compound. View Full-Text
Keywords: dietary compounds; estrogen receptor; breast cancer; gene expression; endocrine disruption dietary compounds; estrogen receptor; breast cancer; gene expression; endocrine disruption
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MDPI and ACS Style

Lecomte, S.; Demay, F.; Pham, T.H.; Moulis, S.; Efstathiou, T.; Chalmel, F.; Pakdel, F. Deciphering the Molecular Mechanisms Sustaining the Estrogenic Activity of the Two Major Dietary Compounds Zearalenone and Apigenin in ER-Positive Breast Cancer Cell Lines. Nutrients 2019, 11, 237. https://doi.org/10.3390/nu11020237

AMA Style

Lecomte S, Demay F, Pham TH, Moulis S, Efstathiou T, Chalmel F, Pakdel F. Deciphering the Molecular Mechanisms Sustaining the Estrogenic Activity of the Two Major Dietary Compounds Zearalenone and Apigenin in ER-Positive Breast Cancer Cell Lines. Nutrients. 2019; 11(2):237. https://doi.org/10.3390/nu11020237

Chicago/Turabian Style

Lecomte, Sylvain, Florence Demay, Thu H. Pham, Solenn Moulis, Théo Efstathiou, Frédéric Chalmel, and Farzad Pakdel. 2019. "Deciphering the Molecular Mechanisms Sustaining the Estrogenic Activity of the Two Major Dietary Compounds Zearalenone and Apigenin in ER-Positive Breast Cancer Cell Lines" Nutrients 11, no. 2: 237. https://doi.org/10.3390/nu11020237

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