Metavanadate suppresses desferrioxamine-induced leukemic cell differentiation with reduced hypoxia-inducible factor-1alpha protein

Biochem Biophys Res Commun. 2005 Jul 15;332(4):1140-5. doi: 10.1016/j.bbrc.2005.05.066.

Abstract

We recently showed that moderate hypoxia and hypoxia-mimetic agents CoCl(2) and desferrioxamine (DFO) induce differentiation of acute myeloid leukemic cells via hypoxia-inducible factor-1alpha (HIF-1alpha) that interacts with and increases the transcriptional activity of CCAAT/enhancer-binding protein alpha (C/EBPalpha), a critical factor for granulocytic differentiation. Here, we show that metavanadate antagonizes DFO-induced growth arrest and differentiation with the inhibition of HIF-1alpha protein accumulation in leukemic cells. Furthermore, DFO also increased C/EBPalpha expression rapidly but transiently, which was inhibited by metavanadate. Taken together, these findings provide further evidence for the role of HIF-1alpha and C/EBPalpha in DFO-induced leukemic cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • COS Cells
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Deferoxamine / pharmacology*
  • Granulocytes / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Leukemia / drug therapy*
  • Leukemia / pathology
  • Luciferases / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation
  • U937 Cells
  • Vanadates / pharmacology*

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Transcription Factors
  • Vanadates
  • Luciferases
  • Deferoxamine