Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production

Página do item simplificado
dc.contributor.authorTamarindo, Guilherme H.
dc.contributor.authorRibeiro, Daniele L.
dc.contributor.authorGobbo, Marina G. [UNESP]
dc.contributor.authorGuerra, Luiz H. A. [UNESP]
dc.contributor.authorRahal, Paula [UNESP]
dc.contributor.authorTaboga, Sebastiao R. [UNESP]
dc.contributor.authorGadelha, Fernanda R.
dc.contributor.authorGoes, Rejane M. [UNESP]
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Federal de Uberlândia (UFU)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2019-10-04T12:34:45Z
dc.date.available2019-10-04T12:34:45Z
dc.date.issued2019-01-01
dc.description.abstractProstate cancer development has been associated with changes in mitochondria' activity and reactive oxygen species (ROS) production. Melatonin (MLT) and docosahexaenoic acid (DHA) have properties to modulate both, but their protective role, mainly at early stages of prostate cancer, remains unclear. In this study, the effects of MLT and DHA, combined or not, on PNT1A cells with regard to mitochondria bioenergetics, ROS production, and proliferation-related pathways were examined. Based on dose response and lipid accumulation assays, DHA at 100 mu M and MLT at 1 mu M for 48 h were chosen. DHA doubled and MLT reduced (40%) superoxide anion production, but coincubation (DM) did not normalize to control. Hydrogen peroxide production decreased after MLT incubation only (p < 0.01). These alterations affected the area and perimeter of mitochondria, since DHA increased whereas MLT decreased, but such hormone has no effect on coincubation. DHA isolated did not change the oxidative phosphorylation rate (OXPHOS), but decreased (p < 0.001) the mitochondria' bioenergetic reserve capacity (MBRC) which is closely related to cell responsiveness to stress conditions. MLT, regardless of DHA, ameliorated OXPHOS and recovered MBRC after coincubation. All incubations decreased AKT phosphorylation; however, only MLT alone inhibited p-mTOR. MLT increased p-ERK1/2 and, when combined to DHA, increased GSTP1 expression (p < 0.01). DHA did not change the testosterone levels in the medium, whereas MLT alone or coincubated decreased by about 20%; however, any incubation affected AR expression. Moreover, incubation with luzindole revealed that MLT effects were MTR1/2-independent. In conclusion, DHA increased ROS production and impaired mitochondrial function which was probably related to AKT inactivation; MLT improved OXPHOS and decreased ROS which was related to AKT/mTOR dephosphorylation, and when coincubated, the antiproliferative action was related to mitochondrial bioenergetic modulation associated to AKT and ERK1/2 regulation. Together, these findings point to the potential application of DHA and MLT towards the prevention of proliferative prostate diseases.en
dc.description.affiliationUniv Estadual Campinas, Inst Biol, Campinas, SP, Brazil
dc.description.affiliationUniv Fed Uberlandia, Inst Biomed Sci, Dept Histol, Uberlandia, MG, Brazil
dc.description.affiliationSao Paulo State Univ, Inst Biosci Humanities & Exact Sci, Dept Biol, Sao Jose Do Rio Preto, SP, Brazil
dc.description.affiliationUniv Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Inst Biosci Humanities & Exact Sci, Dept Biol, Sao Jose Do Rio Preto, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipSao Jose do Rio Preto Extension and Research Foundation (FAPERP)
dc.description.sponsorshipIdCAPES: 001
dc.description.sponsorshipIdSao Jose do Rio Preto Extension and Research Foundation (FAPERP): 002/2018
dc.description.sponsorshipId: 308367/2014-6 - CNPq
dc.description.sponsorshipId: 2013/16368-7
dc.description.sponsorshipId: 2018/19590-6 - FAPESP
dc.description.sponsorshipId: 2015/13371-2 FAPESP
dc.description.sponsorshipId: 2015/24595-9 FAPESP
dc.description.sponsorshipId: 309764/2015-7 CNPq
dc.format.extent15
dc.identifierhttp://dx.doi.org/10.1155/2019/5080798
dc.identifier.citationOxidative Medicine And Cellular Longevity. London: Hindawi Ltd, 15 p., 2019.
dc.identifier.doi10.1155/2019/5080798
dc.identifier.issn1942-0900
dc.identifier.lattes7991082362671212
dc.identifier.lattes0947193347312157
dc.identifier.orcid0000-0001-5693-6148
dc.identifier.orcid0000-0002-3622-460X
dc.identifier.urihttp://hdl.handle.net/11449/185350
dc.identifier.wosWOS:000456643600001
dc.language.isoeng
dc.publisherHindawi Ltd
dc.relation.ispartofOxidative Medicine And Cellular Longevity
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titleMelatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Productionen
dc.typeArtigo
dcterms.rightsHolderHindawi Ltd
unesp.author.lattes7991082362671212[5]
unesp.author.lattes0947193347312157[8]
unesp.author.orcid0000-0001-5693-6148[5]
unesp.author.orcid0000-0002-3622-460X[8]

Arquivos

Coleções

Artigos - Biologia - IBILCE