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.

Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells / A., Leardi; M., Caraglia; Selleri, Carmine; Pepe, Stefano; Pizzi, Claudia; R., Notaro; Fabbrocini, Antonietta; DE LORENZO, Sonya; M., Musico; A., Abbruzzese; Bianco, ANGELO RAFFAELE; P. T. a. g. l. i. a. f. e. r. r., I.. - In: BRITISH JOURNAL OF HAEMATOLOGY. - ISSN 0007-1048. - STAMPA. - 102:3(1998), pp. 746-752.

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

SELLERI, CARMINE;PEPE, STEFANO;PIZZI, CLAUDIA;FABBROCINI, ANTONIETTA;DE LORENZO, SONYA;BIANCO, ANGELO RAFFAELE;
1998

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 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.
1998
Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells / A., Leardi; M., Caraglia; Selleri, Carmine; Pepe, Stefano; Pizzi, Claudia; R., Notaro; Fabbrocini, Antonietta; DE LORENZO, Sonya; M., Musico; A., Abbruzzese; Bianco, ANGELO RAFFAELE; P. T. a. g. l. i. a. f. e. r. r., I.. - In: BRITISH JOURNAL OF HAEMATOLOGY. - ISSN 0007-1048. - STAMPA. - 102:3(1998), pp. 746-752.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/157095
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