title: Proliferative Properties of 17β-aminoestrogens in MCF-7 Human Breast Cancer Cells.
abstract: The 17β-aminoestrogens (AEs) prolame, butolame and pentolame are weakly oestrogenic in rodents and display anticoagulant properties in contrast to oestradiol (E2) which presents pro-coagulant effects, potentially thrombogenic. They possess anti-anxiety and antidepressive properties, being good candidates for menopausal hormone therapy (MHT). Their capability to induce proliferation of MCF-7 human breast cancer cells, in which proliferative rate depends on oestrogens, has not been explored; thus, the aim of this work was to characterize it. AEs' proliferation properties were evaluated compared with E2in MCF-7 carcinoma cell line cultures using established methods. Receptor mediation on cell proliferation was studied by co-incubating them with the oestrogen receptor antagonists tamoxifen, ICI 182,780 and the selective antagonists MPP (ERα) and PHTPP (ERβ). E2and AEs increased MCF-7 cell proliferation; their proliferative effect was between 1.5-2 and E2= 3.6 compared with controls (0); their relative proliferative effect was 18-38% (E2= 100%) with a relative proliferative potency of 4.5-8.9 (E2= 100). The ERα antagonist MPP inhibited the MCF-7 cell proliferation induced by E2and AEs; on the contrary, the ERβ antagonist PHTPP exacerbated the proliferative response, showing that the AEs' proliferative activity was mainly ERα-mediated and apparently controlled by ERβ. Preliminary cytometric DNA flow analysis showed that AEs' cell cycle S phase inducer property was lower than E2following the proliferative order: E2> butolame > prolame > pentolame, indicating pentolame with the weakest proliferative properties and being the safest of this series as a candidate for MHT.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National Autonomous University of México, México City, México.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lemini
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National Autonomous University of México, México City, México.
authors.forename: María
authors.initials: M
authors.lastname: Estela Avila
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National Autonomous University of México, México City, México.
authors.forename: Martha
authors.initials: M
authors.lastname: Medina
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National Autonomous University of México, México City, México.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sánchez
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National Autonomous University of México, México City, México.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Figueroa
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National Autonomous University of México, México City, México.
authors.forename: Maria Juana
authors.initials: MJ
authors.lastname: García-Mondragón
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National Autonomous University of México, México City, México.
authors.forename: Arsenio
authors.initials: A
authors.lastname: Vargas-Vázquez
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National Autonomous University of México, México City, México.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jiménez-Orozco
mesh_terms: D000605:Amino Alcohols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology*; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D015914:Estrogen Replacement Therapy / Q000379:methods; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D017698:Postmenopause / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology
chemical_list: D000605:Amino Alcohols; D004963:Estrenes; D065171:Estrogen Receptor Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020845:Selective Estrogen Receptor Modulators; C083219:butolame; C083220:pentolame; D004958:Estradiol; C047867:prolame