title: Estrogenic activity of 7-hydroxymatairesinol potassium acetate (HMR/lignan) from Norway spruce (Picea abies) knots and of its active metabolite enterolactone in MCF-7 cells.
abstract: Lignans are plant polyphenols which may possess anticancer, antioxidant, antimicrobial, anti-inflammatory and immunomodulatory activities. In particular, the lignan 7-hydroxymatairesinol (HMR/lignan, HMR) is a novel precursor of the mammalian lignan enterolactone (EL). In the present study, we investigated the estrogenicity of HMR and of EL in comparison to estradiol (E2), by measuring their effects on growth and apoptotic markers in the human estrogen-sensitive cell line MCF-7. HMR, EL and E2 concentration-dependently increased the percentage of MCF-7 cells in the S phase of the cell cycle, with the following relative potencies: E2 congruent with EL>>HMR, and efficacies: E2>HMR>>EL. Treatment of MCF-7 cells with either HMR, EL or E2 also increased the Bcl-2/Bax mRNA ratio. The effects of HMR and EL were reduced in the presence of the estrogen receptor (ER) antagonist tamoxifene. We conclude that both HMR and its metabolite EL are endowed with estrogenic activity, which is likely to be exerted through the contribution of ER-dependent pathways and to target the same intracellular mechanisms acted upon by E2. The estrogenicity of HMR and EL is however milder than that of E2, as indicated by the lower potencies and efficacies of both lignans. The present results support the notion that dietary supplementation with HMR may result in a mild estrogenic activity, both directly and by providing a suitable source for endogenous EL.
authors.affiliation: Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology, University of Insubria, Via Ottorino Rossi no. 9, 21100 Varese, VA, Italy. marco.cosentino@uninsubria.it
authors.forename: Marco
authors.initials: M
authors.lastname: Cosentino
authors.forename: Franca
authors.initials: F
authors.lastname: Marino
authors.forename: Marco
authors.initials: M
authors.lastname: Ferrari
authors.forename: Emanuela
authors.initials: E
authors.lastname: Rasini
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bombelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Luini
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Legnaro
authors.forename: Marco Gioacchino
authors.initials: MG
authors.lastname: Delle Canne
authors.forename: Marcello
authors.initials: M
authors.lastname: Luzzani
authors.forename: Francesca
authors.initials: F
authors.lastname: Crema
authors.forename: Silvano
authors.initials: S
authors.lastname: Paracchini
authors.forename: Sergio
authors.initials: S
authors.lastname: Lecchini
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000975:Antioxidants / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D048789:Phytoestrogens / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D028222:Picea / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; C494826:BAX protein, human; D004965:Estrogen Antagonists; D017705:Lignans; D048789:Phytoestrogens; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C419306:hydroxymatairesinol; D013629:Tamoxifen; D004958:Estradiol; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone