title: Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation.
abstract: Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases.
authors.affiliation: Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lecomte
authors.affiliation: Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lelong
authors.affiliation: Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Bourgine
authors.affiliation: Laboratoire Nutrinov, Technopole Atalante Champeaux, 8 rue Jules Maillard de la Gournerie, 35012 Rennes Cedex, France.
authors.forename: Theo
authors.initials: T
authors.lastname: Efstathiou
authors.affiliation: Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Saligaut
authors.affiliation: Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes, France. Electronic address: farzad.pakdel@univ-rennes1.fr.
authors.forename: Farzad
authors.initials: F
authors.lastname: Pakdel
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D061986:MCF-7 Cells; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects*; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048789:Phytoestrogens / Q000494:pharmacology*; D051381:Rats; D020218:Response Elements; D000077185:Resveratrol; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D015025:Zearalenone / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D007529:Isoflavones; D009419:Nerve Tissue Proteins; D048789:Phytoestrogens; D020845:Selective Estrogen Receptor Modulators; D013267:Stilbenes; D015025:Zearalenone; C004742:daidzein; D047310:Apigenin; D000077185:Resveratrol
keywords: Breast cancer cell lines; Differentiation; PC12; Phytoestrogens; Proliferation; SERM