Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.lfs.2023.121530 http://hdl.handle.net/11449/246921 |
Resumo: | Aims: Hepatocellular Carcinoma (HCC) is a primary neoplasm derived from hepatocytes with low responsiveness and recurrent chemoresistance. Melatonin is an alternative agent that may be helpful in treating HCC. We aimed to study in HuH 7.5 cells whether melatonin treatment exerts antitumor effects and, if so, what cellular responses are induced and involved. Main methods: We evaluated the effects of melatonin on cell cytotoxicity and proliferation, colony formation, morphological and immunohistochemical aspects, and on glucose consumption and lactate release. Key findings: Melatonin reduced cell motility and caused lamellar breakdown, membrane damage, and reduction in microvillus. Immunofluorescence analysis revealed that melatonin reduced TGF and N-cadherin expression, which was further associated with inhibition of epithelial-mesenchymal transition process. In relation to the Warburg-type metabolism, melatonin reduced glucose uptake and lactate production by modulating intracellular lactate dehydrogenase activity. Significance: Our results indicate that melatonin can act upon pyruvate/lactate metabolism, preventing the Warburg effect, which may reflect in the cell architecture. We demonstrated the direct cytotoxic and antiproliferative effect of melatonin on the HuH 7.5 cell line, and suggest that melatonin is a promising candidate to be further tested as an adjuvant to antitumor drugs for HCC treatment. |
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Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potentialAdjuvant therapyHuH 7.5 cellLiver cancerWarburg effectAims: Hepatocellular Carcinoma (HCC) is a primary neoplasm derived from hepatocytes with low responsiveness and recurrent chemoresistance. Melatonin is an alternative agent that may be helpful in treating HCC. We aimed to study in HuH 7.5 cells whether melatonin treatment exerts antitumor effects and, if so, what cellular responses are induced and involved. Main methods: We evaluated the effects of melatonin on cell cytotoxicity and proliferation, colony formation, morphological and immunohistochemical aspects, and on glucose consumption and lactate release. Key findings: Melatonin reduced cell motility and caused lamellar breakdown, membrane damage, and reduction in microvillus. Immunofluorescence analysis revealed that melatonin reduced TGF and N-cadherin expression, which was further associated with inhibition of epithelial-mesenchymal transition process. In relation to the Warburg-type metabolism, melatonin reduced glucose uptake and lactate production by modulating intracellular lactate dehydrogenase activity. Significance: Our results indicate that melatonin can act upon pyruvate/lactate metabolism, preventing the Warburg effect, which may reflect in the cell architecture. We demonstrated the direct cytotoxic and antiproliferative effect of melatonin on the HuH 7.5 cell line, and suggest that melatonin is a promising candidate to be further tested as an adjuvant to antitumor drugs for HCC treatment.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Financiadora de Estudos e ProjetosUniversidade Estadual de LondrinaLaboratory of Immunoparasitology of Neglected Diseases and Cancer State University of Londrina, PRDepartment of Surgery Cedars-Sinai Medical CenterUniversidade Estadual do Norte do Paraná (UENP) Centro de Ciências Biológicas, PRLaboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos Universidade Estadual de Maringá (UEM)Department of Structural and Functional Biology Paulista State University — UNESP, SPLaboratory of Toxicological Genetics State University of Londrina, PRUniversidade Estadual do Oeste do Paraná, PRDepartment of Structural and Functional Biology Paulista State University — UNESP, SPUniversidade Estadual de Londrina (UEL)Cedars-Sinai Medical CenterCentro de Ciências BiológicasUniversidade Estadual de Maringá (UEM)Universidade Estadual Paulista (UNESP)Universidade Estadual do Oeste do ParanáCruz, Ellen Mayara SouzaConcato, Virginia Marciade Morais, Juliana Maria BitencourtSilva, Taylon FelipeInoue, Fabricio Seidy Ribeirode Souza Cremer, MilenaBidóia, Danielle LazarinMachado, Rayanne Regina Beltramede Almeida Chuffa, Luiz Gustavo [UNESP]Mantovani, Mário SérgioPanis, CarolinaPavanelli, Wander RogérioSeiva, Fábio Rodrigues Ferreira2023-07-29T12:54:13Z2023-07-29T12:54:13Z2023-04-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.lfs.2023.121530Life Sciences, v. 319.1879-06310024-3205http://hdl.handle.net/11449/24692110.1016/j.lfs.2023.1215302-s2.0-85149251737Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengLife Sciencesinfo:eu-repo/semantics/openAccess2023-07-29T12:54:13Zoai:repositorio.unesp.br:11449/246921Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:22:29.776401Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential |
title |
Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential |
spellingShingle |
Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential Cruz, Ellen Mayara Souza Adjuvant therapy HuH 7.5 cell Liver cancer Warburg effect |
title_short |
Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential |
title_full |
Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential |
title_fullStr |
Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential |
title_full_unstemmed |
Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential |
title_sort |
Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential |
author |
Cruz, Ellen Mayara Souza |
author_facet |
Cruz, Ellen Mayara Souza Concato, Virginia Marcia de Morais, Juliana Maria Bitencourt Silva, Taylon Felipe Inoue, Fabricio Seidy Ribeiro de Souza Cremer, Milena Bidóia, Danielle Lazarin Machado, Rayanne Regina Beltrame de Almeida Chuffa, Luiz Gustavo [UNESP] Mantovani, Mário Sérgio Panis, Carolina Pavanelli, Wander Rogério Seiva, Fábio Rodrigues Ferreira |
author_role |
author |
author2 |
Concato, Virginia Marcia de Morais, Juliana Maria Bitencourt Silva, Taylon Felipe Inoue, Fabricio Seidy Ribeiro de Souza Cremer, Milena Bidóia, Danielle Lazarin Machado, Rayanne Regina Beltrame de Almeida Chuffa, Luiz Gustavo [UNESP] Mantovani, Mário Sérgio Panis, Carolina Pavanelli, Wander Rogério Seiva, Fábio Rodrigues Ferreira |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Londrina (UEL) Cedars-Sinai Medical Center Centro de Ciências Biológicas Universidade Estadual de Maringá (UEM) Universidade Estadual Paulista (UNESP) Universidade Estadual do Oeste do Paraná |
dc.contributor.author.fl_str_mv |
Cruz, Ellen Mayara Souza Concato, Virginia Marcia de Morais, Juliana Maria Bitencourt Silva, Taylon Felipe Inoue, Fabricio Seidy Ribeiro de Souza Cremer, Milena Bidóia, Danielle Lazarin Machado, Rayanne Regina Beltrame de Almeida Chuffa, Luiz Gustavo [UNESP] Mantovani, Mário Sérgio Panis, Carolina Pavanelli, Wander Rogério Seiva, Fábio Rodrigues Ferreira |
dc.subject.por.fl_str_mv |
Adjuvant therapy HuH 7.5 cell Liver cancer Warburg effect |
topic |
Adjuvant therapy HuH 7.5 cell Liver cancer Warburg effect |
description |
Aims: Hepatocellular Carcinoma (HCC) is a primary neoplasm derived from hepatocytes with low responsiveness and recurrent chemoresistance. Melatonin is an alternative agent that may be helpful in treating HCC. We aimed to study in HuH 7.5 cells whether melatonin treatment exerts antitumor effects and, if so, what cellular responses are induced and involved. Main methods: We evaluated the effects of melatonin on cell cytotoxicity and proliferation, colony formation, morphological and immunohistochemical aspects, and on glucose consumption and lactate release. Key findings: Melatonin reduced cell motility and caused lamellar breakdown, membrane damage, and reduction in microvillus. Immunofluorescence analysis revealed that melatonin reduced TGF and N-cadherin expression, which was further associated with inhibition of epithelial-mesenchymal transition process. In relation to the Warburg-type metabolism, melatonin reduced glucose uptake and lactate production by modulating intracellular lactate dehydrogenase activity. Significance: Our results indicate that melatonin can act upon pyruvate/lactate metabolism, preventing the Warburg effect, which may reflect in the cell architecture. We demonstrated the direct cytotoxic and antiproliferative effect of melatonin on the HuH 7.5 cell line, and suggest that melatonin is a promising candidate to be further tested as an adjuvant to antitumor drugs for HCC treatment. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29T12:54:13Z 2023-07-29T12:54:13Z 2023-04-15 |
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/10.1016/j.lfs.2023.121530 Life Sciences, v. 319. 1879-0631 0024-3205 http://hdl.handle.net/11449/246921 10.1016/j.lfs.2023.121530 2-s2.0-85149251737 |
url |
http://dx.doi.org/10.1016/j.lfs.2023.121530 http://hdl.handle.net/11449/246921 |
identifier_str_mv |
Life Sciences, v. 319. 1879-0631 0024-3205 10.1016/j.lfs.2023.121530 2-s2.0-85149251737 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Life Sciences |
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 |
|
_version_ |
1808128639129092096 |