Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/42779

TitleThe cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH
Author(s)Silva, João Sérgio Azevedo Lima
Queirós, Odília
Ribeiro, Ana
Baltazar, Fátima
Ko H. Young
Pedersen, Peter L.
Preto, Ana
Casal, Margarida
Keywords3-bromopyruvate
Cluster of differentiation (CD) 147
Extracellular acid pH
Lactate
Monocarboxylate transporter
Tumour microenvironment
Issue date2015
PublisherBiochemical Society
JournalBiochemical Journal
Abstract(s)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.
TypeArticle
URIhttp://hdl.handle.net/1822/42779
DOI10.1042/BJ20140921
ISSN0264-6021
Publisher versionhttp://www.biochemj.org/bj/imps/abs/BJ20140921.htm
Peer-Reviewedyes
AccessOpen access
Appears in Collections:DBio - Artigos/Papers
ICVS - Artigos em Revistas Internacionais com Referee

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