title: In vitro and in vivo activity of 4-thio-uridylate against JY cells, a model for human acute lymphoid leukemia.
abstract: We have previously reported the in vitro anti-proliferative effect of 4-thio-uridylate (s(4)UMP) on OCM-1 uveal melanoma cells. Here, we assessed the efficacy of s(4)UMP on JY cells. Treatment of JY cells with s(4)UMP suppressed their colony forming activity and induced apoptosis; healthy human bone marrow granulocyte-macrophage progenitor cells were 14-fold less sensitive to the nucleotide. In vivo effectiveness of s(4)UMP was determined using xenograft SCID mouse model. s(4)UMP decreased the cell number and colony forming activity of the total cell content of the femur of SCID mice transplanted with JY cells without affecting the bone marrow of healthy mice. These results suggest that s(4)UMP alone or in combination with other clinically approved anti-leukemic remedies should be further explored as a potential novel therapeutic agent.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei Krt., Debrecen 4032, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Berényi
authors.forename: Ilona
authors.initials: I
authors.lastname: Benko
authors.forename: György
authors.initials: G
authors.lastname: Vámosi
authors.forename: Krisztina
authors.initials: K
authors.lastname: Géresi
authors.forename: Ilona
authors.initials: I
authors.lastname: Tárkányi
authors.forename: István
authors.initials: I
authors.lastname: Szegedi
authors.forename: Levente
authors.initials: L
authors.lastname: Lukács
authors.forename: István
authors.initials: I
authors.lastname: Juhász
authors.forename: Csongor
authors.initials: C
authors.lastname: Kiss
authors.forename: László
authors.initials: L
authors.lastname: Fésüs
authors.forename: János
authors.initials: J
authors.lastname: Aradi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015448:Leukemia, B-Cell / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D013234:Stem Cells / Q000187:drug effects; D013873:Thionucleotides / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D013873:Thionucleotides; C009473:4-thiouridylic acid; D014542:Uridine Monophosphate