title: Oleocanthal Modulates Estradiol-Induced Gene Expression Involving Estrogen Receptor α.
abstract: Oleocanthal is a bioactive compound from olive oil. It has attracted considerable attention as it is anti-inflammatory, antiproliferative, and has been shown to possess neuroprotective properties in vitro and in vivo. Delineated from its polyphenolic structure, the aim of this study was to characterize oleocanthal towards estrogenic properties. This might contribute to partly explain the beneficial effects described for the Mediterranean diet. Estrogenic properties of oleocanthal were assessed by different methods: a) stimulation of reporter gene activity in MVLN or RNDA cells either expressing estrogen receptor α or β, b) stimulation of luciferase reporter gene activity in U2OS osteosarcoma cells expressing estrogen receptor α or β, and c) elucidation of the impact on estradiol-induced gene expression in U2OS cells transduced with both estrogen receptors. Depending on the cell line origin, oleocanthal inhibited luciferase activity (MVLN, U2OS-estrogen receptor β) or weakly induced reporter gene activity at 10 µM in U2OS-estrogen receptor α cells. However, oleocanthal inhibited stimulation of luciferase activity by estradiol from both estrogen receptors. Oleocanthal, if given alone, did not stimulate gene expression in U2OS cells, but it significantly modulated the response of estradiol. Oleocanthal enhanced the effect of estradiol on the regulation of those genes, which are believed to be regulated through heterodimeric estrogen receptors. As the estrogenic response pattern of oleocanthal is rather unique, we compared the results obtained with oleacein. Oleocanthal binds to both estrogen receptors inducing estradiol-agonistic or antiagonistic effects depending on the cell line. Regarding regulation of gene expression in U2OS-estrogen receptor α/β cells, oleocanthal and oleacein enhanced estradiol-mediated regulation of heterodimer-regulated genes.
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, Dresden, Germany.
authors.forename: Annekathrin Martina
authors.initials: AM
authors.lastname: Keiler
authors.affiliation: Department of Animal Biology and Physiology, University of Yaoundé I, Yaoundé, Cameroon.
authors.forename: Sefirin
authors.initials: S
authors.lastname: Djiogue
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, Dresden, Germany.
authors.forename: Tino
authors.initials: T
authors.lastname: Ehrhardt
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, Dresden, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zierau
authors.affiliation: Division of Pharmacognosy, University of Athens, Panepistimioupolis, Zographou, Athens, Greece.
authors.forename: Leandros
authors.initials: L
authors.lastname: Skaltsounis
authors.affiliation: Division of Pharmacognosy, University of Athens, Panepistimioupolis, Zographou, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Halabalaki
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, Dresden, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Vollmer
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D001141:Aromatase / Q000235:genetics; D002460:Cell Line / Q000187:drug effects; D000081004:Cyclopentane Monoterpenes; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D010636:Phenols / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D020218:Response Elements / Q000187:drug effects / Q000235:genetics; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000235:genetics; D000099189:Lysophospholipase D
chemical_list: D000447:Aldehydes; D001141:Aromatase; D000081004:Cyclopentane Monoterpenes; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; D010727:Phosphoric Diester Hydrolases; D020845:Selective Estrogen Receptor Modulators; D014841:von Willebrand Factor; D000099189:Lysophospholipase D; C506487:ESR1 protein, human; C578055:oleacein; C503534:oleocanthal; C561410:CYP19A1 protein, human