Summary
Erythroid differentiation of human leukemic K 562 cells is inhibited by the iron chelator desferrioxamine (DF). In addition, desferrioxamine induces an increase of uptake of hemin. When hemin is added to the culture medium, the DF-mediated inhibitory effects on erythroid induction are reversed. Briefly, hemin allows hemoglobin synthesis by K 562 cells induced to erythroid differentiation by 1-β-D-arabinofuranosylcytosine (ara-C) and treated with 12.5 μg/ml DF. In addition, it was found that hemin treatment leads to a reversion of inhibition of K 562 cell proliferation mediated by 50–75 μg/ml DF. This effect of hemin was also detected in other cultured human tumor cell lines (B-lymphoid, erythroleukemic and from breast carcinomas, melanomas and kidney carcinomas).
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References
Baralle FE, Schoulders CC, Proudfoot NJ (1980) The Primary Structure of the Human ɛ-Globin Gene. Cell 21: 621–626
Bianchi Scarrà GL, Romani M, Coviello DA, Garrè C, Ravazzolo R, Vidali G, Ajmar F (1986) Terminal Erythroid Differentiation in the K-562 Cell Line by 1-β-D-Arabinofuranosylcytosine: Accompaniment by c-myc Messenger RNA decrease. Cancer Res 46: 6327–6332
Cioè L, McNab A, Hubbell HR, Meo P, Curtis P, Rovera G (1981) Differential expression of globin genes in human leukemia K 562 (S) cells induced to differentiate by hemin or butyric acid. Cancer Res 41: 237–243
Dobner PR, Kawasaki ES, Yu LJ, Bancroft FC (1981) Thyroid or glucocorticoid hormone induces pre-growth hormone mRNA and its probable nuclear precursor in rat pituitary cells. Proc Natl Acad Sci USA 78: 2230–2234
Galbraith RA, Sassa S, Kappas A (1985) Heme binding to Murine Erythroleukemia Cells. J Biol Chem 260: 12198–12202
Gambari R (1983) Desferrioxamine-mediated inhibition of heme and hemoglobin synthesis in murine erythroleukemia cells: expression of globin genes and commitment to erythroid differentiation. Cell Biol Int Rep 7: 785–795
Gambari R, Raschellà G, Tripodi M, Farace MG, Fantoni A (1983) Desferrioxamine inhibits induced erythroid differentiation of human leukemic K 562 cells. Cell Differ 12: 249–255
Gambari R, del Senno L, Barbieri R, Viola L, Tripodi M, Raschellà G, Fantoni A (1984) Human leukemia K 562 cells: induction of erythroid differentiation by 5-azacytidine. Cell Differ 14: 87–97
Gambari R, del Senno L, Piva R, Barbieri R, Amelotti F, Bernardi F, Marchetti G, Citarella F, Tripodi M, Fantoni A (1984) Human leukemia K 562 cells: relationship between hemin-mediated erythroid induction, cell proliferation and expression of c-abl and c-myc oncogenes. Biochem Biophys Res Commun 125: 90–95
Gambari R, Barbieri R, Buzzoni D, Bernardi F, Marchetti G, Amelotti F, Piva R, Viola L, del Senno L (1986) Human leukemic K 562 cells: suppression of hemoglobin accumulation by a monoclonal antibody to human transferrin receptor. Biochim Biophys Acta 886: 203–213
Giacomini P, Imberti L, Aguzzi A, Fisher PB, Trinchieri G, Ferrone S (1985) Immunochemical analysis of the modulation of human melanoma associated antigens by DNA recombinant immune interferon. J Immunol 135: 2887–2891
Hautanen A, Linden P (1981) C 3 c-Binding ELISA for the Detection of Immunoconglutinins and Immunoglobulin aggregates. Methods Enzymol 74: 588–607
Kontoghiorghes GJ, Piga A, Hoffbrand AV (1986) Cytotoxic and DNA-Inhibitory Effects of Iron Chelators on Human Leukemic Cell Lines. Haematol Oncol 4: 195–204
Larrick JW, Hyman ES (1984) Acquired iron-deficiency anemia caused by an antibody against the transferrin receptor. N Engl J Med 311: 214–218
Lozzio CB, Lozzio BB (1975) Human chronic myelogenous leukemia cell line with positive Philadelphia chromosome. Blood 45: 321–334
Luisi De Luca C, Mitchell T, Spriggs D, Kufe DW (1984) Induction of terminal differentiation in human K 562 erythroleukemia cells by arabinofuranosylcytosine. J Clin Invest 74: 821–827
Quaranta V, Pellegrino MA, Ferrone S (1981) Serological and immunochemical characterization of the specificity of four monoclonal antibodies to distinct antigenic determinants expressed on subpopulation of human Ia-like antigens. J Immunol 126: 548–552
Robbins E, Peterson T (1970) Iron: its intracellular localization and possible role in cell division. Proc Natl Acad Sci USA 66: 1244–1251
Rouault T, Rao K, Harfold J, Mattia E, Klausner RD (1986) Hemin, Chelatable Iron, and the Regulation of Transferrin Receptor Biosynthesis. J Biol Chem 260: 14862–14866
Schmidt JA, Marschall J, Hayman MJ, Ponka P, Beug H (1986) Control of Erythroid Differentiation: Possible Role of the Transferrin Cycle. Cell 46: 41–51
Shibahara S, Muller RM, Taguchi H (1987) Transcriptional control of rat heme oxygenase by heat shock. J Biol Chem 262: 12889–12892
Smith A, Morgan WT (1979) Haem transport to the liver by haemopexin. Biochem J 182: 47–54
Trowbridge IS, Omary MB (1981) Human cell surface glycoprotein related to cell proliferation is the receptor for transferrin. Proc Natl Acad Sci USA 78: 3039–3043
Wilson RL (1977) Iron, zinc, free radicals and oxygen in tissue disorders and cancer control. In: Iron metabolism. CIBA Symposium, vol 51, Elsevier, Excerpta Medica, North Holland, pp 331–349
White B, Bancroft F (1982) Cytoplasmic dot hybridization; Simple analysis of relative mRNA levels in multiple small cell or tissue sample. J Biol Chem 257: 8562–8572
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Feriotto, G., Nastruzzi, C., Barbieri, R. et al. Induction to erythroid differentiation of K 562 cells by 1-β-D-arabinofuranosylcytosine is inhibited by iron chelators: reversion by treatment with hemin. Blut 57, 25–30 (1988). https://doi.org/10.1007/BF00320631
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DOI: https://doi.org/10.1007/BF00320631