Decavanadate and metformin-decavanadate effects in human melanoma cells
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
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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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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1799133329418616832 |