Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells

Authors

  • Annalisa Leardi,

    1. Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy,
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  • Michele Caraglia,

    1. Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy,
    2. Dipartimento di Biochimica e Biofisica, Seconda Università di Napoli, Naples, Italy
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  • Carmine Selleri,

    1. Cattedra di Ematologia Clinica, Dipartimento di Medicina Interna e Malattie Dismetaboliche, Università Federico II, Naples, Italy,
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  • Stefano Pepe,

    1. Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy,
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  • Claudia Pizzi,

    1. Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy,
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  • Rosario Notaro,

    1. Cattedra di Ematologia Clinica, Dipartimento di Medicina Interna e Malattie Dismetaboliche, Università Federico II, Naples, Italy,
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  • Antonietta Fabbrocini,

    1. Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy,
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  • Sonya De Lorenzo,

    1. Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy,
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  • Manuela MusicÒ,

    1. Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy,
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  • Alberto Abbruzzese,

    1. Dipartimento di Biochimica e Biofisica, Seconda Università di Napoli, Naples, Italy
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  • Angelo Raffaele Bianco,

    1. Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy,
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  • Pierosandro Tagliaferri

    1. Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy,
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Dr Pierosandro Tagliaferri Cattedra di Oncologia Medica, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Abstract

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 n M ara-C for 48 h 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.

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