Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/molecules27144350 http://hdl.handle.net/11449/240427 |
Resumo: | Ovarian cancer (OC) is the most lethal gynecologic malignancy, and melatonin has shown various antitumor properties. Herein, we investigated the influence of melatonin therapy on energy metabolism and mitochondrial integrity in SKOV-3 cells and tested whether its effects depended on MT1 receptor activation. SKOV-3 cells were exposed to different melatonin concentrations, and experimental groups were divided as to the presence of MT1 receptors (melatonin groups) or receptor absence by RNAi silencing (siRNA MT1+melatonin). Intracellular melatonin levels increased after treatment with melatonin independent of the MT1. The mitochondrial membrane potential of SKOV-3 cells decreased in the group treated with the highest melatonin concentration. Melatonin reduced cellular glucose consumption, while MT1 knockdown increased its consumption. Interconversion of lactate to pyruvate increased after treatment with melatonin and was remarkable in siRNA MT1 groups. Moreover, lactate dehydrogenase activity decreased with melatonin and increased after MT1 silencing at all concentrations. The UCSC XenaBrowser tool showed a positive correlation between the human ASMTL gene and the ATP synthase genes, succinate dehydrogenase gene (SDHD), and pyruvate dehydrogenase genes (PDHA and PDHB). We conclude that melatonin changes the glycolytic phenotype and mitochondrial integrity of SKOV-3 cells independent of the MT1 receptor, thus decreasing the survival advantage of OC cells. |
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Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activationglucosemelatoninmitochondrial metabolismovarian cancerSKOV-3 cellsWarburg effectOvarian cancer (OC) is the most lethal gynecologic malignancy, and melatonin has shown various antitumor properties. Herein, we investigated the influence of melatonin therapy on energy metabolism and mitochondrial integrity in SKOV-3 cells and tested whether its effects depended on MT1 receptor activation. SKOV-3 cells were exposed to different melatonin concentrations, and experimental groups were divided as to the presence of MT1 receptors (melatonin groups) or receptor absence by RNAi silencing (siRNA MT1+melatonin). Intracellular melatonin levels increased after treatment with melatonin independent of the MT1. The mitochondrial membrane potential of SKOV-3 cells decreased in the group treated with the highest melatonin concentration. Melatonin reduced cellular glucose consumption, while MT1 knockdown increased its consumption. Interconversion of lactate to pyruvate increased after treatment with melatonin and was remarkable in siRNA MT1 groups. Moreover, lactate dehydrogenase activity decreased with melatonin and increased after MT1 silencing at all concentrations. The UCSC XenaBrowser tool showed a positive correlation between the human ASMTL gene and the ATP synthase genes, succinate dehydrogenase gene (SDHD), and pyruvate dehydrogenase genes (PDHA and PDHB). We conclude that melatonin changes the glycolytic phenotype and mitochondrial integrity of SKOV-3 cells independent of the MT1 receptor, thus decreasing the survival advantage of OC cells.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Structural and Functional Biology Institute of Biosciences UNESP—São Paulo State University, São PauloCancer Molecular Research Laboratory (LIMC) FAMERP Department of Molecular Biology, São PauloBiological Science Center Department of Biology Luiz Meneghel Campus Universidade Estadual do Norte do Paraná—UENP, ParanáDepartment of Cell Systems and Anatomy UT HealthDepartment of Structural and Functional Biology Institute of Biosciences UNESP—São Paulo State University, São PauloFAPESP: 2018/15797-5FAPESP: 2019/00906-6Universidade Estadual Paulista (UNESP)FAMERPUniversidade Estadual do Norte do Paraná—UENPUT HealthCucielo, Maira Smaniotto [UNESP]Cesário, Roberta Carvalho [UNESP]Silveira, Henrique Spaulonci [UNESP]Gaiotte, Letícia Barbosa [UNESP]Santos, Sérgio Alexandre Alcantara dos [UNESP]Zuccari, Debora Aparecida Pires de CamposSeiva, Fábio Rodrigues FerreiraReiter, Russel J.Chuffa, Luiz Gustavo de Almeida [UNESP]2023-03-01T20:16:41Z2023-03-01T20:16:41Z2022-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/molecules27144350Molecules, v. 27, n. 14, 2022.1420-3049http://hdl.handle.net/11449/24042710.3390/molecules271443502-s2.0-85133782148Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMoleculesinfo:eu-repo/semantics/openAccess2023-03-01T20:16:41Zoai:repositorio.unesp.br:11449/240427Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:19:51.156863Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation |
title |
Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation |
spellingShingle |
Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation Cucielo, Maira Smaniotto [UNESP] glucose melatonin mitochondrial metabolism ovarian cancer SKOV-3 cells Warburg effect |
title_short |
Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation |
title_full |
Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation |
title_fullStr |
Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation |
title_full_unstemmed |
Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation |
title_sort |
Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation |
author |
Cucielo, Maira Smaniotto [UNESP] |
author_facet |
Cucielo, Maira Smaniotto [UNESP] Cesário, Roberta Carvalho [UNESP] Silveira, Henrique Spaulonci [UNESP] Gaiotte, Letícia Barbosa [UNESP] Santos, Sérgio Alexandre Alcantara dos [UNESP] Zuccari, Debora Aparecida Pires de Campos Seiva, Fábio Rodrigues Ferreira Reiter, Russel J. Chuffa, Luiz Gustavo de Almeida [UNESP] |
author_role |
author |
author2 |
Cesário, Roberta Carvalho [UNESP] Silveira, Henrique Spaulonci [UNESP] Gaiotte, Letícia Barbosa [UNESP] Santos, Sérgio Alexandre Alcantara dos [UNESP] Zuccari, Debora Aparecida Pires de Campos Seiva, Fábio Rodrigues Ferreira Reiter, Russel J. Chuffa, Luiz Gustavo de Almeida [UNESP] |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) FAMERP Universidade Estadual do Norte do Paraná—UENP UT Health |
dc.contributor.author.fl_str_mv |
Cucielo, Maira Smaniotto [UNESP] Cesário, Roberta Carvalho [UNESP] Silveira, Henrique Spaulonci [UNESP] Gaiotte, Letícia Barbosa [UNESP] Santos, Sérgio Alexandre Alcantara dos [UNESP] Zuccari, Debora Aparecida Pires de Campos Seiva, Fábio Rodrigues Ferreira Reiter, Russel J. Chuffa, Luiz Gustavo de Almeida [UNESP] |
dc.subject.por.fl_str_mv |
glucose melatonin mitochondrial metabolism ovarian cancer SKOV-3 cells Warburg effect |
topic |
glucose melatonin mitochondrial metabolism ovarian cancer SKOV-3 cells Warburg effect |
description |
Ovarian cancer (OC) is the most lethal gynecologic malignancy, and melatonin has shown various antitumor properties. Herein, we investigated the influence of melatonin therapy on energy metabolism and mitochondrial integrity in SKOV-3 cells and tested whether its effects depended on MT1 receptor activation. SKOV-3 cells were exposed to different melatonin concentrations, and experimental groups were divided as to the presence of MT1 receptors (melatonin groups) or receptor absence by RNAi silencing (siRNA MT1+melatonin). Intracellular melatonin levels increased after treatment with melatonin independent of the MT1. The mitochondrial membrane potential of SKOV-3 cells decreased in the group treated with the highest melatonin concentration. Melatonin reduced cellular glucose consumption, while MT1 knockdown increased its consumption. Interconversion of lactate to pyruvate increased after treatment with melatonin and was remarkable in siRNA MT1 groups. Moreover, lactate dehydrogenase activity decreased with melatonin and increased after MT1 silencing at all concentrations. The UCSC XenaBrowser tool showed a positive correlation between the human ASMTL gene and the ATP synthase genes, succinate dehydrogenase gene (SDHD), and pyruvate dehydrogenase genes (PDHA and PDHB). We conclude that melatonin changes the glycolytic phenotype and mitochondrial integrity of SKOV-3 cells independent of the MT1 receptor, thus decreasing the survival advantage of OC cells. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-07-01 2023-03-01T20:16:41Z 2023-03-01T20:16:41Z |
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/10.3390/molecules27144350 Molecules, v. 27, n. 14, 2022. 1420-3049 http://hdl.handle.net/11449/240427 10.3390/molecules27144350 2-s2.0-85133782148 |
url |
http://dx.doi.org/10.3390/molecules27144350 http://hdl.handle.net/11449/240427 |
identifier_str_mv |
Molecules, v. 27, n. 14, 2022. 1420-3049 10.3390/molecules27144350 2-s2.0-85133782148 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Molecules |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus 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 |
|
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1808129310294278144 |