ArticleBritish journal of pharmacology2014
Nucleoside transporters and human organic cation transporter 1 determine the cellular handling of DNA-methyltransferase inhibitors.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review.Targeted oncology · 2018Pooled it
- Zebularine Boosts Imatinib Efficacy in Cells of Colorectal Cancer via Wnt-Survivin-P-Glycoprotein Pathway.Journal of biochemical and molecular toxicology · 2026Article
- Nucleoside transporters and immunosuppressive adenosine signaling in the tumor microenvironment: Potential therapeutic opportunities.Pharmacology & therapeutics · 2022Review
- Solute Carrier Nucleoside Transporters in Hematopoiesis and Hematological Drug Toxicities: A Perspective.Cancers · 2022Review
- Predicting Drug Interactions with Human Equilibrative Nucleoside Transporters 1 and 2 Using Functional Knockout Cell Lines and Bayesian Modeling.Molecular pharmacology · 2021Article
- Article
- Identification of volasertib-resistant mechanism and evaluation of combination effects with volasertib and other agents on acute myeloid leukemia.Oncotarget · 2017Article
- Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia.International journal of nanomedicine · 2017Article
- Role of SLC22A1 polymorphic variants in drug disposition, therapeutic responses, and drug-drug interactions.The pharmacogenomics journal · 2015Review
- Acquired resistance to decitabine and cross-resistance to gemcitabine during the long-term treatment of human HCT116 colorectal cancer cells with decitabine.Oncology letters · 2015Article
- Nucleoside transporter proteins as biomarkers of drug responsiveness and drug targets.Frontiers in pharmacology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeInhibitors 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
resultsZebularine 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.
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