Decavanadate and metformin-decavanadate effects in human melanoma cells

Detalhes bibliográficos
Autor(a) principal: de Sousa-Coelho, Ana Luísa
Data de Publicação: 2022
Outros Autores: Aureliano, Manuel, Fraqueza, Gil, Serrão, Gisela, Gonçalves, João, Sánchez-Lombardo, Irma, Link, Wolfgang, Ferreira, Bibiana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/18596
Resumo: Decavanadate is a polyoxometalate (POMs) that has shown extensive biological activities, including antidiabetic and anticancer activity. Importantly, vanadium-based compounds as well as antidiabetic biguanide drugs, such as metformin, have shown to exert therapeutic effects in melanoma. A combination of these agents, the metformin-decavanadate complex, was also recognized for its antidiabetic effects and recently described as a better treatment than the monotherapy with metformin enabling lower dosage in rodent models of diabetes. Herein, we compare the effects of decavanadate and metformin-decavanadate on Ca2+-ATPase activity in sarcoplasmic reticulum vesicles from rabbit skeletal muscles and on cell signaling events and viability in human melanoma cells. We show that unlike the decavanadate-mediated non-competitive mechanism, metformin-decavanadate inhibits Ca2+-ATPase by a mixed-type competitive-non-competitive inhibition with an IC50 value about 6 times higher (87 mu M) than the previously described for decavanadate (15 mu M). We also found that both decavanadate and metformin-decavanadate exert antiproliferative effects on melanoma cells at 10 times lower concentrations than monomeric vanadate. Western blot analysis revealed that both, decavanadate and metformin-decavanadate increased phosphorylation of extracellular signal-regulated kinase (ERK) and serine/ threonine protein kinase AKT signaling proteins upon 24 h drug exposure, suggesting that the anti-proliferative activities of these compounds act independent of growth-factor signaling pathways.
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spelling Decavanadate and metformin-decavanadate effects in human melanoma cellsDecavanadateMetforminMetformin-decavanadatePolyoxometalatesPolyoxovanadatesSkin cancerMelanomaCell signalingDecavanadate is a polyoxometalate (POMs) that has shown extensive biological activities, including antidiabetic and anticancer activity. Importantly, vanadium-based compounds as well as antidiabetic biguanide drugs, such as metformin, have shown to exert therapeutic effects in melanoma. A combination of these agents, the metformin-decavanadate complex, was also recognized for its antidiabetic effects and recently described as a better treatment than the monotherapy with metformin enabling lower dosage in rodent models of diabetes. Herein, we compare the effects of decavanadate and metformin-decavanadate on Ca2+-ATPase activity in sarcoplasmic reticulum vesicles from rabbit skeletal muscles and on cell signaling events and viability in human melanoma cells. We show that unlike the decavanadate-mediated non-competitive mechanism, metformin-decavanadate inhibits Ca2+-ATPase by a mixed-type competitive-non-competitive inhibition with an IC50 value about 6 times higher (87 mu M) than the previously described for decavanadate (15 mu M). We also found that both decavanadate and metformin-decavanadate exert antiproliferative effects on melanoma cells at 10 times lower concentrations than monomeric vanadate. Western blot analysis revealed that both, decavanadate and metformin-decavanadate increased phosphorylation of extracellular signal-regulated kinase (ERK) and serine/ threonine protein kinase AKT signaling proteins upon 24 h drug exposure, suggesting that the anti-proliferative activities of these compounds act independent of growth-factor signaling pathways.ElsevierSapientiade Sousa-Coelho, Ana LuísaAureliano, ManuelFraqueza, GilSerrão, GiselaGonçalves, JoãoSánchez-Lombardo, IrmaLink, WolfgangFerreira, Bibiana2022-12-07T11:24:33Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/18596eng0162-013410.1016/j.jinorgbio.2022.111915info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:30:52Zoai:sapientia.ualg.pt:10400.1/18596Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:08:20.388433Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Decavanadate and metformin-decavanadate effects in human melanoma cells
title Decavanadate and metformin-decavanadate effects in human melanoma cells
spellingShingle Decavanadate and metformin-decavanadate effects in human melanoma cells
de Sousa-Coelho, Ana Luísa
Decavanadate
Metformin
Metformin-decavanadate
Polyoxometalates
Polyoxovanadates
Skin cancerMelanoma
Cell signaling
title_short Decavanadate and metformin-decavanadate effects in human melanoma cells
title_full Decavanadate and metformin-decavanadate effects in human melanoma cells
title_fullStr Decavanadate and metformin-decavanadate effects in human melanoma cells
title_full_unstemmed Decavanadate and metformin-decavanadate effects in human melanoma cells
title_sort Decavanadate and metformin-decavanadate effects in human melanoma cells
author de Sousa-Coelho, Ana Luísa
author_facet de Sousa-Coelho, Ana Luísa
Aureliano, Manuel
Fraqueza, Gil
Serrão, Gisela
Gonçalves, João
Sánchez-Lombardo, Irma
Link, Wolfgang
Ferreira, Bibiana
author_role author
author2 Aureliano, Manuel
Fraqueza, Gil
Serrão, Gisela
Gonçalves, João
Sánchez-Lombardo, Irma
Link, Wolfgang
Ferreira, Bibiana
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Sapientia
dc.contributor.author.fl_str_mv de Sousa-Coelho, Ana Luísa
Aureliano, Manuel
Fraqueza, Gil
Serrão, Gisela
Gonçalves, João
Sánchez-Lombardo, Irma
Link, Wolfgang
Ferreira, Bibiana
dc.subject.por.fl_str_mv Decavanadate
Metformin
Metformin-decavanadate
Polyoxometalates
Polyoxovanadates
Skin cancerMelanoma
Cell signaling
topic Decavanadate
Metformin
Metformin-decavanadate
Polyoxometalates
Polyoxovanadates
Skin cancerMelanoma
Cell signaling
description Decavanadate is a polyoxometalate (POMs) that has shown extensive biological activities, including antidiabetic and anticancer activity. Importantly, vanadium-based compounds as well as antidiabetic biguanide drugs, such as metformin, have shown to exert therapeutic effects in melanoma. A combination of these agents, the metformin-decavanadate complex, was also recognized for its antidiabetic effects and recently described as a better treatment than the monotherapy with metformin enabling lower dosage in rodent models of diabetes. Herein, we compare the effects of decavanadate and metformin-decavanadate on Ca2+-ATPase activity in sarcoplasmic reticulum vesicles from rabbit skeletal muscles and on cell signaling events and viability in human melanoma cells. We show that unlike the decavanadate-mediated non-competitive mechanism, metformin-decavanadate inhibits Ca2+-ATPase by a mixed-type competitive-non-competitive inhibition with an IC50 value about 6 times higher (87 mu M) than the previously described for decavanadate (15 mu M). We also found that both decavanadate and metformin-decavanadate exert antiproliferative effects on melanoma cells at 10 times lower concentrations than monomeric vanadate. Western blot analysis revealed that both, decavanadate and metformin-decavanadate increased phosphorylation of extracellular signal-regulated kinase (ERK) and serine/ threonine protein kinase AKT signaling proteins upon 24 h drug exposure, suggesting that the anti-proliferative activities of these compounds act independent of growth-factor signaling pathways.
publishDate 2022
dc.date.none.fl_str_mv 2022-12-07T11:24:33Z
2022
2022-01-01T00:00:00Z
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://hdl.handle.net/10400.1/18596
url http://hdl.handle.net/10400.1/18596
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0162-0134
10.1016/j.jinorgbio.2022.111915
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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