The α1-adrenergic receptor antagonists, benoxathian and prazosin, induce apoptosis and a switch towards megakaryocytic differentiation in human erythroleukemia cells

Robert Fuchs (1) , Ingeborg Stelzer (1) , Helga S. Haas (1) , Gerd Leitinger (2, 3) , Konrad Schauenstein (1) , Anton Sadjak (1)

1 Institute of Pathophysiology and Immunology, Center of Molecular Medicine
2 Institute of Cell Biology, Histology and Embryology, Center of Molecular Medicine
3 Center for Medical Research, Core Facility Ultrastructure Analysis

The erythroleukemia cell lines K562 and human erythroleukemia (HEL) are established models to study erythroid and megakaryocytic differentiation . In this study, we show that the α1-adrenergic antagonists, benoxathian and prazosin, inhibit the proliferation and induce apoptosis in K562 and HEL cells. Furthermore, both tested substances induced the expression of the megakaryocytic marker CD41a, whereas the expression of the erythroid marker glycophorin-a was decreased or unchanged. Even though the expression of differentiation markers was similar after benoxathian and prazosin treatment in both cell lines, endomitosis of erythroleukemia cells was observed only after prazosin treatment. So far, benoxathian and prazosin are the first described extracellular ligands, which cause megakaryocytic differentiation in K562 and HEL cells. In summary, these results indicate a possible role of α1-adrenergic receptor signaling in the regulation of erythroid and megakaryocytic differentiation, even though the receptor dependence of the observed effects needs further investigation.

Mots clés: Erythroleukemia cells; α1-adrenergic antagonists; Apoptosis; Erythroid differentiation; Megakaryocytic differentiation

Robert Fuchs, Ingeborg Stelzer, Helga S. Haas, Gerd Leitinger, Konrad Schauenstein, et al.. The α1-adrenergic receptor antagonists, benoxathian and prazosin, induce apoptosis and a switch towards megakaryocytic differentiation in human erythroleukemia cells. Annals of Hematology, 2009, 88 (10), pp.989-997. ⟨10.1007/s00277-009-0704-z⟩. ⟨hal-00535032⟩