Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells.
We investigated whether changes in iron metabolism and the transferrin receptor (TRF-R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara-C). Treatment with 100 nM ara-C for 48h reduced thymidine uptake and increased the surface expression of the TRF-R on leukaemic blasts derived from 13/16 (81%) patients and on the HL-60 and U-937 cell lines. Whereas intracellular non-haem iron was strongly depleted 24 h after ara-C addition, TRF-R up-regulation and recovery of intracellular non-haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara-C and the iron chelator desferioxamine (DSF) on the growth of HL-60 and U-937 cells. We found that desferioxamine strongly potentiated the effects of ara-C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara-C and an iron chelator in terms of antileukaemic effects.
Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy.
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Leardi
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Caraglia
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Selleri
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Pepe
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Pizzi
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Notaro
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Fabbrocini
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De Lorenzo
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Musicò
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Abbruzzese
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Bianco
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Tagliaferri
D000208:Acute Disease; D000931:Antidotes / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000378:metabolism / Q000627:therapeutic use*; D003676:Deferoxamine / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D007501:Iron / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011990:Receptors, Transferrin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D011990:Receptors, Transferrin; D003561:Cytarabine; D007501:Iron; D003676:Deferoxamine