In vitro and in vivo activity of 4-thio-uridylate against JY cells, a model for human acute lymphoid leukemia

Biochem Biophys Res Commun. 2011 Jul 8;410(3):682-7. doi: 10.1016/j.bbrc.2011.06.056. Epub 2011 Jun 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Leukemia, B-Cell / drug therapy*
  • Mice
  • Mice, SCID
  • Stem Cells / drug effects
  • Thionucleotides / chemistry
  • Thionucleotides / pharmacokinetics
  • Thionucleotides / therapeutic use*
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / chemistry
  • Uridine Monophosphate / pharmacokinetics
  • Uridine Monophosphate / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Thionucleotides
  • 4-thiouridylic acid
  • Uridine Monophosphate