Differentiating activity of adriamycin in human erythroleukemic cells: effect on globin and heme synthesis

Abstract

The human leukemic cell line K 562 can be induced to differentiate along the erythroid lineage by various chemical compounds and particularly by the anthracyclic antitumor drug, adriamycin (ADR). In this study, we show that, in the presence of a subtoxic concentration of ADR (30 nM), the appearance of hemoglobin-producing K 562 cells is associated with a specific increase in globin mRNA accumulation corresponding to ɛ-, χ-, γ-, α-globin chains. At the translational level, bulk protein synthesis is strongly decreased following ADR treatment, whereas globin chain synthesis is specifically enhanced. Globin chains represent about 20% of total proteins in ADR-treated cells, versus about 3.5% in controls on day 3. Similarly, on day 3, heme synthesis ( 55Fe incorporation) is about 10-times higher in ADR-treated cells than in control cells (20 888 dpm/10 5 cells versus 1693 dpm/10 5 cells) which confirms the increase in heme content (420 pM/10 6 treated cells versus 100 pM/10 6 control cells). In the presence of succinylacetone, a heme synthesis inhibitor which prevented the differentiating effects of ADR, the globin mRNA accumulation was not affected. This suggests that heme did not play a regulatory role in globin mRNA transcription, a result at variance with observations published by others. Such results strongly support the notion that in addition to cytostatic properties, ADR stimulates specifically globin and heme synthesis.