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Nucleoside transporters and human organic cation transporter 1 determine the cellular handling of DNA-methyltransferase inhibitors

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dc.contributor Universitat de Vic. Càtedra de la Sida i Malalties Relacionades
dc.contributor.author Arimany Nardi, C.
dc.contributor.author Errasti-Murugarren, E.
dc.contributor.author Minuesa, G.
dc.contributor.author Martinez Picado, Francisco Javier
dc.contributor.author Gorboulev, V.
dc.contributor.author Koepsell, H.
dc.contributor.author Pastor-Anglada, M.
dc.date.accessioned 2014-09-17T07:09:14Z
dc.date.available 2014-09-17T07:09:14Z
dc.date.created 2014
dc.date.issued 2014
dc.identifier.citation Arimany-Nardi, C., Errasti-Murugarren, E., Minuesa, G., Martínez-Picado, J., Gorboulev, V., Koepsell, H., et al. (2014). Nucleoside transporters and human organic cation transporter 1 determine the cellular handling of DNA-methyltransferase inhibitors. British Journal of Pharmacology, 171(16), 3868-3880.10.1111/bph.12748 ca_ES
dc.identifier.issn 0007-1188
dc.identifier.uri http://hdl.handle.net/10854/3263
dc.description.abstract BACKGROUND AND PURPOSE Inhibitors of DNA methyltransferases (DNMTs), such as azacytidine, decitabine and zebularine, are used for the epigenetic treatment of cancer. Their action may depend upon their translocation across the plasma membrane. The aim of this study was to identify transporter proteins contributing to DNMT inhibitor action. EXPERIMENTAL APPROACH Drug interactions with selected hCNT and hENT proteins were studied in transiently transfected HeLa and MDCK cells. Interaction with human organic cation transporters (hOCTs) was assessed in transiently transfected HeLa cells and Xenopus laevis oocytes. KEY RESULTS Zebularine uptake was mediated by hCNT1, hCNT3 and hENT2. Decitabine interacted with but was not translocated by any nucleoside transporter (NT) type. hCNT expression at the apical domain of MDCK cells promoted net vectorial flux of zebularine. Neither hOCT1 nor hOCT2 transported decitabine, but both were involved in the efflux of zebularine, suggesting these proteins act as efflux transporters. hOCT1 polymorphic variants, known to alter function, decreased zebularine efflux. CONCLUSIONS AND IMPLICATIONS This study highlights the influence of human NTs and hOCTs on the pharmacokinetics and pharmacodynamics of selected DNMT inhibitors. As hOCTs may also behave as efflux transporters, they could contribute either to chemoresistance or to chemosensitivity, depending upon the nature of the drug or combination of drugs being used in cancer therapy. en
dc.format application/pdf
dc.format.extent 13 p. ca_ES
dc.language.iso eng ca_ES
dc.publisher Wiley ca_ES
dc.rights Tots els drets reservats
dc.rights (c) Blackwell Wiley [The definitive version is available at www3.interscience.wiley.com] ca_ES
dc.subject.other Càncer ca_ES
dc.title Nucleoside transporters and human organic cation transporter 1 determine the cellular handling of DNA-methyltransferase inhibitors en
dc.type info:eu-repo/semantics/article ca_ES
dc.identifier.doi https://doi.org/0.1111/bph.12748
dc.relation.publisherversion http://onlinelibrary.wiley.com/doi/10.1111/bph.12748/abstract;jsessionid=1CC649C92C6A654B4167289B3131E416.f04t04
dc.rights.accesRights info:eu-repo/semantics/closedAccess ca_ES
dc.type.version info:eu-repo/publishedVersion ca_ES
dc.indexacio Indexat a SCOPUS ca_ES

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