Iron chelators induce apoptosis in proliferating cells.
The iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (L1) and desferrioxamine (DFO) were found to induce apoptosis of proliferating activated T-lymphocytes and of the promyelocytic cell line HL60, but not of resting peripheral blood lymphocytes or granulocytes. The induction of apoptosis was quantified by propidium iodide staining of apoptotic/dead cells and flow cytometry. In activated T-lymphocytes incubated with the chelators at equivalent iron-binding concentrations (300 microM L1 or 100 microM DFO) for 24 h, L1 caused a 54% increase in cell death and DFO a 57% increase. In HL60 cells L1 caused a 50% increase in cell death and DFO a 40% increase. DNA cytofluorometry of HL60 cells treated with either chelator showed an increase in the percentage of cells with hypodiploid DNA content. Presaturation of the chelators with ferric chloride abrogated these effects. L1 and DFO did not induce apoptosis in resting peripheral blood lymphocytes or granulocytes, even after 48 h of incubation.
Department of Haematology, Royal Free Hospital School of Medicine, London.
D
D
Hileti
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Panayiotidis
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Hoffbrand
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division; D002478:Cells, Cultured; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects; D014407:Tumor Cells, Cultured
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D003676:Deferoxamine