The role of human nucleoside transporters in cellular uptake of 4'-thio-beta-D-arabinofuranosylcytosine and beta-D-arabinosylcytosine

Molecular Pharmacology
Marilyn L ClarkeCarol E Cass

Abstract

4'-Thio-beta-D-arabinofuranosyl cytosine (TaraC) is in phase I development for treatment of cancer. In human equilibrative nucleoside transporter (hENT) 1-containing CEM cells, initial rates of uptake (10 microM; picomoles per microliter of cell water per second) of [3H]TaraC and [3H]1-beta-D-arabinofuranosyl cytosine (araC) were low (0.007 +/- 003 and 0.034 +/- 0.003, respectively) compared with that of [3H]uridine (0.317 +/- 0.048), a highactivity hENT1 permeant. In hENT1- and hENT2-containing HeLa cells, initial rates of uptake (10 microM; picomoles per cell per second) of [3H]TaraC, [3H]araC, and [3H]deoxycytidine were low (0.30 +/- 0.003, 0.42 +/- 0.03, and 0.51 +/- 0.11, respectively) and mediated primarily by hENT1 (approximately 74, approximately 65, and approximately 61%, respectively). In HeLa cells with recombinant human concentrative nucleoside transporter (hCNT) 1 or hCNT3 and pharmacologically blocked hENT1 and hENT2, transport of 10 microM[3H]TaraC and [3H]araC was not detected. The apparent affinities of recombinant transporters (produced in yeast) for a panel of cytosine-containing nucleosides yielded results that were consistent with the observed low-permeant activities of TaraC and araC for hENT1/2 and neglig...Continue Reading

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Citations

Mar 9, 2007·Cancer Metastasis Reviews·Jing ZhangCarol E Cass
Feb 26, 2015·Frontiers in Pharmacology·Marçal Pastor-Anglada, Sandra Pérez-Torras
Jul 20, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Balázs VaskóPeter Krajcsi
Aug 1, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J D YoungS A Baldwin
Aug 1, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M Pastor-AngladaF J Casado
Nov 13, 2008·Cancer Chemotherapy and Pharmacology·William B ParkerWilliam R Waud
Feb 26, 2010·Nucleosides, Nucleotides & Nucleic Acids·Vijaya L DamarajuCarol E Cass
May 28, 2010·Pharmacogenomics·Ekaitz Errasti-Murugarren, Marçal Pastor-Anglada
Feb 3, 2011·Medicinal Research Reviews·Pedro Cano-Soldado, Marçal Pastor-Anglada
Aug 4, 2012·Future Medicinal Chemistry·Jung-Suk Choi, Anthony J Berdis
Apr 17, 2013·Clinical Pharmacology and Therapeutics·K M HillgrenUNKNOWN International Transporter Consortium
Dec 14, 2019·Pharmacology Research & Perspectives·Jason T AndersonAlex Sparreboom
Sep 1, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Rajgopal GovindarajanJashvant D Unadkat
Feb 18, 2017·Cancer Research·Christina D DrenbergAlex Sparreboom
Sep 4, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Katja A PuttonenAtso Raasmaja

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