title: Anti-tumor mechanisms of 3'-ethynyluridine and 3'-ethynylcytidine as RNA synthesis inhibitors: development and characterization of 3'-ethynyluridine-resistant cells.
abstract: To discover the mechanisms of anti-tumor action of 3'-ethynyluridine (EUrd) and 3'-ethynylcytidine (ECyd), we established an EUrd-resistant variant from human fibrosarcoma HT-1080 cells. The cells were cross-resistant to ECyd. Uridine/cytidine kinase activity diminished in the resistant cells. The incorporation of EUrd and ECyd into the RNA fraction in the resistant cells was less than that of the parental cells. EUrd-triphosphate inhibited RNA synthesis by human RNA polymerase II. The results led us to conclude that EUrd and ECyd are phosphorylated by uridine/cytidine kinase to 5'-triphosphates, and that their triphosphates might inhibit RNA polymerase.
authors.affiliation: Department of Experimental Therapeutics, Cancer Research Institute, Kanazawa University, Takaramachi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tabata
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Obata
authors.forename: A
authors.initials: A
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004351:Drug Resistance; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C103084:1-(3-C-ethynylribopentofuranosyl)cytosine; C103085:1-(3-C-ethynylribopentofuranosyl)uracil; D000964:Antimetabolites, Antineoplastic; D019384:Nucleic Acid Synthesis Inhibitors; D003562:Cytidine; D012313:RNA; D004247:DNA; D014529:Uridine