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Keywords:

  • angelicin;
  • erythroid differentiation;
  • γ-globin;
  • fetal hemoglobin;
  • β-thalassemia;
  • sickle cell anemia

Abstract:

The aim of the present study was to determine whether angelicin is able to increase the expression of γ-globin genes in human erythroid cells. Angelicin is structurally related to psoralens, a well-known chemical class of photosensitizers used for their antiproliferative activity in treatment of different skin diseases (i.e., psoriasis and vitiligo). To verify the activity of angelicin, we employed two experimental cell systems, the human leukemic K562 cell line and the two-phase liquid culture of human erythroid progenitors isolated from normal donors. The results of our investigation suggest that angelicin, compared with cytosine arabinoside, mithramycin and cisplatin, is a powerful inducer of erythroid differentiation and γ-globin mRNA accumulation of human leukemia K562 cells. In addition, when normal human erythroid precursors were cultured in the presence of angelicin, increases of γ-globin mRNA accumulation and fetal hemoglobin (HbF) production, even higher than those obtained using hydroxyurea, were detected. These results could have practical relevance, as pharmacologically-mediated regulation of the expression of human γ-globin genes, leading to HbF induction, is considered a potential therapeutic approach in hematological disorders, including β-thalassemia and sickle cell anemia.