Finasteride Inhibits Human Prostate Cancer Cell Invasion through MMP2 and MMP9 Downregulation

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dc.contributor.authorMoroz, Andrei[UNESP]
dc.contributor.authorDelella, Flavia K. [UNESP]
dc.contributor.authorAlmeida, Rodrigo [UNESP]
dc.contributor.authorLacorte, Livia Maria [UNESP]
dc.contributor.authorFavaro, Wagner Jose
dc.contributor.authorDeffune, Elenice [UNESP]
dc.contributor.authorFelisbino, Sergio L. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.date.accessioned2014-12-03T13:10:37Z
dc.date.available2014-12-03T13:10:37Z
dc.date.issued2013-12-30
dc.description.abstractIntroduction: The use of the 5-alpha reductase inhibitors (5-ARIs) finasteride and dutasteride for prostate cancer prevention is still under debate. The FDA recently concluded that the increased prevalence of high-grade tumors among 5-ARI-treated patients must not be neglected, and they decided to disallow the use of 5-ARIs for prostate cancer prevention. This study was conducted to verify the effects of finasteride on prostate cell migration and invasion and the related enzymes/proteins in normal human and tumoral prostatic cell lines.Materials and Methods: RWPE-1, LNCaP, PC3 and DU145 cells were cultivated to 60% confluence and exposed for different periods to either 10 mu M or 50 mu M finasteride that was diluted in culture medium. The conditioned media were collected and concentrated, and MMP2 and MMP9 activities and TIMP-1 and TIMP-2 protein expression were determined. Cell viability, migration and invasion were analyzed, and the remaining cell extracts were submitted to androgen receptor (AR) detection by western blotting techniques. Experiments were carried out in triplicate.Results: Cell viability was not significantly affected by finasteride exposure. Finasteride significantly downregulated MMP2 and MMP9 activities in RWPE-1 and PC3 cells and MMP2 in DU145 cells. TIMP-2 expression in RWPE-1 cells was upregulated after exposure. The cell invasion of all four tested cell lines was inhibited by exposure to 50 mM of finasteride, and migration inhibition only occurred for RWPE-1 and LNCaP cells. AR was expressed by LNCaP, RWPE-1 and PC3 cells.Conclusions: Although the debate on the higher incidence of high-grade prostate cancer among 5-ARI-treated patients remains, our findings indicate that finasteride may attenuate tumor aggressiveness and invasion, which could vary depending on the androgen responsiveness of a patient's prostate cells.en
dc.description.affiliationUniv Estadual Paulista, UNESP, Inst Biosci, Dept Morphol,Extracellular Matrix Lab, Sao Paulo, Brazil
dc.description.affiliationUniv Estadual Paulista, UNESP, Botucatu Med Sch, Blood Transfus Ctr,Cell Engn Lab, Sao Paulo, Brazil
dc.description.affiliationUniv Estadual Campinas, UNICAMP, Inst Biol, Dept Struct & Funct Biol, Sao Paulo, Brazil
dc.description.affiliationUniv Estadual Paulista, UNESP, Botucatu Med Sch, Dept Urol, Sao Paulo, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, UNESP, Inst Biosci, Dept Morphol,Extracellular Matrix Lab, Sao Paulo, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, UNESP, Botucatu Med Sch, Blood Transfus Ctr,Cell Engn Lab, Sao Paulo, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, UNESP, Botucatu Med Sch, Dept Urol, Sao Paulo, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdFAPESP: 10/16671-3
dc.format.extent11
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0084757
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 8, n. 12, 11 p., 2013.
dc.identifier.doi10.1371/journal.pone.0084757
dc.identifier.fileWOS000329194700116.pdf
dc.identifier.issn1932-6203
dc.identifier.lattes9646764071339214
dc.identifier.urihttp://hdl.handle.net/11449/112322
dc.identifier.wosWOS:000329194700116
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPLOS ONE
dc.relation.ispartofjcr2.766
dc.relation.ispartofsjr1,164
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titleFinasteride Inhibits Human Prostate Cancer Cell Invasion through MMP2 and MMP9 Downregulationen
dc.typeArtigo
dcterms.rightsHolderPublic Library Science
unesp.author.lattes9646764071339214
unesp.author.lattes6926124203948011[1]
unesp.author.orcid0000-0002-4498-9784[1]
unesp.author.orcid0000-0001-6362-5882[2]
unesp.author.orcid0000-0001-5830-8938[5]
unesp.author.orcid0000-0002-0533-3248[6]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Medicina, Botucatupt

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