Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1155/2019/5080798 http://hdl.handle.net/11449/185350 |
Resumo: | Prostate 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. |
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Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS ProductionProstate 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Sao Jose do Rio Preto Extension and Research Foundation (FAPERP)Univ Estadual Campinas, Inst Biol, Campinas, SP, BrazilUniv Fed Uberlandia, Inst Biomed Sci, Dept Histol, Uberlandia, MG, BrazilSao Paulo State Univ, Inst Biosci Humanities & Exact Sci, Dept Biol, Sao Jose Do Rio Preto, SP, BrazilUniv Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP, BrazilSao Paulo State Univ, Inst Biosci Humanities & Exact Sci, Dept Biol, Sao Jose Do Rio Preto, SP, BrazilCAPES: 001Sao Jose do Rio Preto Extension and Research Foundation (FAPERP): 002/2018: 308367/2014-6 - CNPq: 2013/16368-7: 2018/19590-6 - FAPESP: 2015/13371-2 FAPESP: 2015/24595-9 FAPESP: 309764/2015-7 CNPqHindawi LtdUniversidade Estadual de Campinas (UNICAMP)Universidade Federal de Uberlândia (UFU)Universidade Estadual Paulista (Unesp)Tamarindo, Guilherme H.Ribeiro, Daniele L.Gobbo, Marina G. [UNESP]Guerra, Luiz H. A. [UNESP]Rahal, Paula [UNESP]Taboga, Sebastiao R. [UNESP]Gadelha, Fernanda R.Goes, Rejane M. [UNESP]2019-10-04T12:34:45Z2019-10-04T12:34:45Z2019-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article15http://dx.doi.org/10.1155/2019/5080798Oxidative Medicine And Cellular Longevity. London: Hindawi Ltd, 15 p., 2019.1942-0900http://hdl.handle.net/11449/18535010.1155/2019/5080798WOS:000456643600001799108236267121209471933473121570000-0001-5693-61480000-0002-3622-460XWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengOxidative Medicine And Cellular Longevityinfo:eu-repo/semantics/openAccess2021-10-23T19:02:00Zoai:repositorio.unesp.br:11449/185350Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T19:02Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production |
title |
Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production |
spellingShingle |
Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production Tamarindo, Guilherme H. |
title_short |
Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production |
title_full |
Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production |
title_fullStr |
Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production |
title_full_unstemmed |
Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production |
title_sort |
Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production |
author |
Tamarindo, Guilherme H. |
author_facet |
Tamarindo, Guilherme H. Ribeiro, Daniele L. Gobbo, Marina G. [UNESP] Guerra, Luiz H. A. [UNESP] Rahal, Paula [UNESP] Taboga, Sebastiao R. [UNESP] Gadelha, Fernanda R. Goes, Rejane M. [UNESP] |
author_role |
author |
author2 |
Ribeiro, Daniele L. Gobbo, Marina G. [UNESP] Guerra, Luiz H. A. [UNESP] Rahal, Paula [UNESP] Taboga, Sebastiao R. [UNESP] Gadelha, Fernanda R. Goes, Rejane M. [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Universidade Federal de Uberlândia (UFU) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Tamarindo, Guilherme H. Ribeiro, Daniele L. Gobbo, Marina G. [UNESP] Guerra, Luiz H. A. [UNESP] Rahal, Paula [UNESP] Taboga, Sebastiao R. [UNESP] Gadelha, Fernanda R. Goes, Rejane M. [UNESP] |
description |
Prostate 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. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-04T12:34:45Z 2019-10-04T12:34:45Z 2019-01-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1155/2019/5080798 Oxidative Medicine And Cellular Longevity. London: Hindawi Ltd, 15 p., 2019. 1942-0900 http://hdl.handle.net/11449/185350 10.1155/2019/5080798 WOS:000456643600001 7991082362671212 0947193347312157 0000-0001-5693-6148 0000-0002-3622-460X |
url |
http://dx.doi.org/10.1155/2019/5080798 http://hdl.handle.net/11449/185350 |
identifier_str_mv |
Oxidative Medicine And Cellular Longevity. London: Hindawi Ltd, 15 p., 2019. 1942-0900 10.1155/2019/5080798 WOS:000456643600001 7991082362671212 0947193347312157 0000-0001-5693-6148 0000-0002-3622-460X |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Oxidative Medicine And Cellular Longevity |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
15 |
dc.publisher.none.fl_str_mv |
Hindawi Ltd |
publisher.none.fl_str_mv |
Hindawi Ltd |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1803046779925561344 |