Evidence for distinct regulation processes in the aclacinomycin- and doxorubicin-mediated differentiation of human erythroleukemic cells

• Published in: Biochemical pharmacology 1996-03, Vol.51 (6), p.839-845
• Main Authors: Morceau, Franck, Aries, Anne, Lahlil, Rachid, Devy, Laetitia, Jardillier, Jean-Claude, Jeannesson, Pierre, Trentesaux, Chantal
• Format: Article
• Language: English
• Subjects: aclacinomycin; Aclarubicin - analogs & derivatives; Aclarubicin - pharmacology; Antibiotics, Antineoplastic - pharmacology; Antineoplastic agents; Base Sequence; Biological and medical sciences; Cell Differentiation - drug effects; Chemotherapy; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; doxorubicin; Doxorubicin - pharmacology; erythroid genes; Erythroid-Specific DNA-Binding Factors; GATA-1; GATA1 Transcription Factor; Gene Expression - drug effects; Globins - biosynthesis; Globins - genetics; Hemoglobins - biosynthesis; Humans; Hydroxymethylbilane Synthase - biosynthesis; Hydroxymethylbilane Synthase - genetics; K 562; Leukemia, Erythroblastic, Acute - drug therapy; Leukemia, Erythroblastic, Acute - metabolism; Leukemia, Erythroblastic, Acute - pathology; Medical sciences; Molecular Sequence Data; NF-E2; NF-E2 Transcription Factor; NF-E2 Transcription Factor, p45 Subunit; Pharmacology. Drug treatments; Receptors, Erythropoietin - biosynthesis; Receptors, Erythropoietin - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transcription Factors - biosynthesis; Transcription Factors - genetics; Tumor Cells, Cultured
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(95)02240-6

Human erythroleukemic K 562 cells were induced to differentiate along the erythroid lineage by anthracycline antitumor drugs, such as aclacinomycin (ACLA) and doxorubicin (DOX). Subsequent stimulation of heme and globin synthesis led to a differential quantitative expression of hemoglobins. Gower 1 ( ϵ 2, ζ 2) was the major type for ACLA and X ( ϵ 2, γ 2) for DOX. Although ACLA and DOX increased both the expression of γ-globin and porphobilinogen deaminase mRNAs, striking differences were observed in the expression of erythropoietin receptor mRNAs and in erythroid transcription factors GATA-1 and NF-E2, known to play a key role in erythroid gene regulation. Indeed, ACLA induces an increase either in the binding capacity of GATA-1 and NF-E2 or in the accumulation of erythropoietin receptor, GATA-1 and NF-E2 transcripts. In contrast, their expression with DOX was not significantly modified compared to uninduced cells, except for a slight decrease in NF-E2 expression on day 3. In conclusion, these data show that: 1. increased expression of erythroid transcription factors and erythroid genes are associated only with ACLA treatment, and 2. although cytotoxicity of both ACLA and DOX is certainly dependent on DNA intercalation, regulation of differentiation processes by these two drugs involves distinct mechanisms.