Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/48249
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dc.contributor.authorMarrero-Alonso, Jorge
dc.contributor.authorMorales, Araceli
dc.contributor.authorGarcía Marrero, Benito
dc.contributor.authorBoto, Alicia
dc.contributor.authorMarín, Raquel
dc.contributor.authorCury, Débora
dc.contributor.authorGómez, Tomás
dc.contributor.authorFernández-Pérez, Leandro
dc.contributor.authorLahoz, Fernando
dc.contributor.authorDíaz, Mario
dc.date.accessioned2018-11-23T20:08:36Z-
dc.date.available2018-11-23T20:08:36Z-
dc.date.issued2013
dc.identifier.issn0939-6411
dc.identifier.urihttp://hdl.handle.net/10553/48249-
dc.description.abstractTamoxifen is a selective estrogen receptor modulator extensively used on estrogen receptor-positive breast cancer treatment. However, clinical evidences demonstrate the increased incidence of undesirable side effects during chronic therapies, the most life threatening being uterine cancers. Some of these effects are related to tissue-dependent estrogenic actions of tamoxifen, but the exact mechanisms remain poorly understood. We have designed and synthesized a novel fluorescent tamoxifen derivative, FLTX1, and characterized its biological and pharmacological activities. Using confocal microscopy, we demonstrate that FLTX1 colocalizes with estrogen receptor alpha (ER alpha). Competition studies showed that FLTX1 binding was totally displaced by unlabeled tamoxifen and partially by estradiol, indicating the existence of non-ER-related triphenylethylene-binding sites. Ligand binding assays showed that FLTX1 exhibits similar affinity for ER than tamoxifen. FLTX1 exhibited antiestrogenic activity comparable to tamoxifen in MCF7 and T47D cells transfected with 3xERE-luciferase reporter. Interestingly, FLTX1 lacked the strong agonistic effect of tamoxifen on ER alpha-dependent transcriptional activity. Additionally, in vivo assays in mice revealed that unlike tamoxifen, FLTX1 was devoid of estrogenic uterotrophic effects, lacked of hyperplasic and hypertrophic effects, and failed to alter basal proliferating cell nuclear antigen immunoreactivity. In the rat uterine model of estrogenicity/antiestrogenicity, FLTX1 displayed antagonistic activity comparable to tamoxifen at lower doses, and only estrogenic uterotrophy at the highest dose. We conclude that the fluorescent derivative FLTX1 is not only a suitable probe for studies on the molecular pharmacology of tamoxifen, but also a potential therapeutic substitute to tamoxifen, endowed with potent antiestrogenic properties but devoid of uterine estrogenicity. (C) 2013 Elsevier B.V. All rights reserved.
dc.publisher0939-6411
dc.relation.ispartofEuropean Journal of Pharmaceutics and Biopharmaceutics
dc.sourceEuropean Journal of Pharmaceutics and Biopharmaceutics[ISSN 0939-6411],v. 85, p. 898-910
dc.subject.otherEstrogen-Receptor Modulators
dc.subject.otherDrug-Dye Complex
dc.subject.otherBreast-Cancer
dc.subject.otherAntiestrogen Tamoxifen
dc.subject.otherMolecular-Mechanisms
dc.subject.otherTissue-Specificity
dc.subject.otherStably Expresses
dc.subject.otherAcute Relaxation
dc.subject.otherCell-Line
dc.subject.otherMouse
dc.titleUnique SERM-like properties of the novel fluorescent tamoxifen derivative FLTX1
dc.typeinfo:eu-repo/semantics/Articlees
dc.typeArticlees
dc.identifier.doi10.1016/j.ejpb.2013.04.024
dc.identifier.scopus84889092473
dc.identifier.isi000330200800010
dc.contributor.authorscopusid12752675300
dc.contributor.authorscopusid14037747600
dc.contributor.authorscopusid12753123700
dc.contributor.authorscopusid6603924488
dc.contributor.authorscopusid7101784493
dc.contributor.authorscopusid54379715900
dc.contributor.authorscopusid35866137000
dc.contributor.authorscopusid6506777525
dc.contributor.authorscopusid55161203400
dc.contributor.authorscopusid7402043998
dc.description.lastpage910
dc.description.firstpage898
dc.relation.volume85
dc.type2Artículoes
dc.contributor.daisngid3824467
dc.contributor.daisngid2645189
dc.contributor.daisngid5810087
dc.contributor.daisngid552679
dc.contributor.daisngid34938311
dc.contributor.daisngid9220643
dc.contributor.daisngid31449249
dc.contributor.daisngid795544
dc.contributor.daisngid465738
dc.contributor.daisngid503429
dc.contributor.wosstandardWOS:Marrero-Alonso, J
dc.contributor.wosstandardWOS:Morales, A
dc.contributor.wosstandardWOS:Marrero, BG
dc.contributor.wosstandardWOS:Boto, A
dc.contributor.wosstandardWOS:Marin, R
dc.contributor.wosstandardWOS:Cury, D
dc.contributor.wosstandardWOS:Gomez, T
dc.contributor.wosstandardWOS:Fernandez-Perez, L
dc.contributor.wosstandardWOS:Lahoz, F
dc.contributor.wosstandardWOS:Diaz, M
dc.date.coverdateEnero 2013
dc.identifier.ulpgces
item.fulltextSin texto completo-
item.grantfulltextnone-
crisitem.author.deptFarmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Ciencias Clínicas-
crisitem.author.orcid0000-0001-7802-465X-
crisitem.author.orcid0000-0003-3878-3867-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameFernández Pérez, Leandro Fco-
crisitem.author.fullNameDiaz Cabrera, Moises-
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