Metavanadate suppresses desferrioxamine-induced leukemic cell differentiation with reduced hypoxia-inducible factor-1alpha protein.
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.
Xue
Zhi-Hong
ZH
Department of Pathophysiology, Rui-Jin Hospital, Shanghai Second Medical University (SSMU), Shanghai 200025, China.
Jiang
Yi
Y
Yu
Yun
Y
Wang
Li-Shun
LS
Chen
Guo-Qiang
GQ
Zhao
Qian
Q
D000818:Animals; D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D019556:COS Cells; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003676:Deferoxamine / Q000494:pharmacology*; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020298:U937 Cells; D014638:Vanadates / Q000494:pharmacology*
D022763:CCAAT-Enhancer-Binding Protein-alpha; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D014638:Vanadates; D008156:Luciferases; D003676:Deferoxamine