The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH
Autor(a) principal: | |
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Data de Publicação: | 2015 |
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/1822/42779 |
Resumo: | Although the anti-cancer properties of 3BP have been described previously, its selectivity for cancer cells still needs to be explained. In the work reported here we characterized the kinetic parameters of radiolabelled [14C]-3BP uptake in three breast cancer cell lines that display different levels of resistance to 3BP: ZR-75-1 < MCF-7 < SK-BR-3. At pH 6.0 the affinity of cancer cells for 3BP transport, correlates with their sensitivity, a pattern that does not occur at pH 7.4. In the three cell lines, the uptake of 3BP is dependent on the proton motive force and is decreased by MCTs inhibitors. In the SK-BR-3 cell line, a sodium-dependent transport also occurs. Butyrate promotes the localization of MCT-1 at the plasma membrane and increases the level of MCT-4 expression, leading to a higher sensitivity for 3BP. Here, we demonstrate that this phenotype is accompanied by an increase in affinity for 3BP uptake. Our results confirm the role of MCTs, especially MCT-1 in 3BP uptake and the importance of CD147 glycosylation in this process. We find that the affinity for 3BP transport is higher when the extracellular milieu is acid. This is a typical phenotype of tumor microenvironment and explains the lack of secondary effects of 3BP already described in in vivo studies. |
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The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH3-bromopyruvateCluster of differentiation (CD) 147Extracellular acid pHLactateMonocarboxylate transporterTumour microenvironmentScience & TechnologyAlthough the anti-cancer properties of 3BP have been described previously, its selectivity for cancer cells still needs to be explained. In the work reported here we characterized the kinetic parameters of radiolabelled [14C]-3BP uptake in three breast cancer cell lines that display different levels of resistance to 3BP: ZR-75-1 < MCF-7 < SK-BR-3. At pH 6.0 the affinity of cancer cells for 3BP transport, correlates with their sensitivity, a pattern that does not occur at pH 7.4. In the three cell lines, the uptake of 3BP is dependent on the proton motive force and is decreased by MCTs inhibitors. In the SK-BR-3 cell line, a sodium-dependent transport also occurs. Butyrate promotes the localization of MCT-1 at the plasma membrane and increases the level of MCT-4 expression, leading to a higher sensitivity for 3BP. Here, we demonstrate that this phenotype is accompanied by an increase in affinity for 3BP uptake. Our results confirm the role of MCTs, especially MCT-1 in 3BP uptake and the importance of CD147 glycosylation in this process. We find that the affinity for 3BP transport is higher when the extracellular milieu is acid. This is a typical phenotype of tumor microenvironment and explains the lack of secondary effects of 3BP already described in in vivo studies.FEDER (Fundo Europeu deDesenvolvimento Regional), through POFC (Programa Operacional Factores de Competitividade) – COMPETE, and by Portuguese National Funds from FCT (Fundac¸˜ao para a Ciˆencia e Tecnologia) in the scope of the project PEst-OE/BIA/U14050/2014. JAS [grant number SFRH/BD/76038/2011] received a fellowship from the Portuguese government from the FCT through FSE (Fundo Social Europeu) and POPH (Programa Operacional Potencial Humano).Biochemical SocietyUniversidade do MinhoSilva, João Sérgio Azevedo LimaQueirós, OdíliaRibeiro, AnaBaltazar, FátimaKo H. YoungPedersen, Peter L.Preto, AnaCasal, Margarida20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/42779eng0264-602110.1042/BJ2014092125641640http://www.biochemj.org/bj/imps/abs/BJ20140921.htminfo: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:RCAAP2023-07-21T12:50:41Zoai:repositorium.sdum.uminho.pt:1822/42779Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:49:24.741114Repositório 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 |
The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH |
title |
The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH |
spellingShingle |
The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH Silva, João Sérgio Azevedo Lima 3-bromopyruvate Cluster of differentiation (CD) 147 Extracellular acid pH Lactate Monocarboxylate transporter Tumour microenvironment Science & Technology |
title_short |
The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH |
title_full |
The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH |
title_fullStr |
The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH |
title_full_unstemmed |
The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH |
title_sort |
The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH |
author |
Silva, João Sérgio Azevedo Lima |
author_facet |
Silva, João Sérgio Azevedo Lima Queirós, Odília Ribeiro, Ana Baltazar, Fátima Ko H. Young Pedersen, Peter L. Preto, Ana Casal, Margarida |
author_role |
author |
author2 |
Queirós, Odília Ribeiro, Ana Baltazar, Fátima Ko H. Young Pedersen, Peter L. Preto, Ana Casal, Margarida |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Silva, João Sérgio Azevedo Lima Queirós, Odília Ribeiro, Ana Baltazar, Fátima Ko H. Young Pedersen, Peter L. Preto, Ana Casal, Margarida |
dc.subject.por.fl_str_mv |
3-bromopyruvate Cluster of differentiation (CD) 147 Extracellular acid pH Lactate Monocarboxylate transporter Tumour microenvironment Science & Technology |
topic |
3-bromopyruvate Cluster of differentiation (CD) 147 Extracellular acid pH Lactate Monocarboxylate transporter Tumour microenvironment Science & Technology |
description |
Although the anti-cancer properties of 3BP have been described previously, its selectivity for cancer cells still needs to be explained. In the work reported here we characterized the kinetic parameters of radiolabelled [14C]-3BP uptake in three breast cancer cell lines that display different levels of resistance to 3BP: ZR-75-1 < MCF-7 < SK-BR-3. At pH 6.0 the affinity of cancer cells for 3BP transport, correlates with their sensitivity, a pattern that does not occur at pH 7.4. In the three cell lines, the uptake of 3BP is dependent on the proton motive force and is decreased by MCTs inhibitors. In the SK-BR-3 cell line, a sodium-dependent transport also occurs. Butyrate promotes the localization of MCT-1 at the plasma membrane and increases the level of MCT-4 expression, leading to a higher sensitivity for 3BP. Here, we demonstrate that this phenotype is accompanied by an increase in affinity for 3BP uptake. Our results confirm the role of MCTs, especially MCT-1 in 3BP uptake and the importance of CD147 glycosylation in this process. We find that the affinity for 3BP transport is higher when the extracellular milieu is acid. This is a typical phenotype of tumor microenvironment and explains the lack of secondary effects of 3BP already described in in vivo studies. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z |
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/1822/42779 |
url |
http://hdl.handle.net/1822/42779 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0264-6021 10.1042/BJ20140921 25641640 http://www.biochemj.org/bj/imps/abs/BJ20140921.htm |
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 |
Biochemical Society |
publisher.none.fl_str_mv |
Biochemical Society |
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 |
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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 |
repository.mail.fl_str_mv |
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1799133075163054080 |