TSP763 - Deciphering the molecular mechanisms sustaining the estrogenic activity of the two major dietary compounds zearalenone and apigenin in ER-positive breast cancer cells Public

Two major compounds found in the diet are the flavone apigenin and the mycotoxin zearalenone. These compounds are able to bind estrogen receptors (ERs) and therefore influence ERs activity. However, the underlying mechanisms are not well known. In this study, we proposed to unravel the molecular mechanisms that could explain the differential effect of zearalenone and apigenin on ER positive breast cancer cell proliferation. Zearalenone clearly enhanced cellular proliferation, while apigenin appeared to be antiestrogenic in the presence of E2. 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, although both zearalenone and apigenin regulate similar set of genes regulated also by E2, the transcription dynamics in gene regulation induced by apigenin were somehow different with zearalenone and E2. These differences in the intensity of gene regulation may explain the differential effect of zearalenone and apigenin on the phenotype of breast cancer cell. Together, our results confirmed the potential therapeutic adjuvant role of apigenin, while zearalenone appeared to be a true endocrine-disrupting compound.