Accumulation of gamma-globin mRNA in human erythroid cells treated with angelicin.
The aim of the present study was to determine whether angelicin is able to increase the expression of gamma-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 gamma-globin mRNA accumulation of human leukemia K562 cells. In addition, when normal human erythroid precursors were cultured in the presence of angelicin, increases of gamma-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 gamma-globin genes, leading to HbF induction, is considered a potential therapeutic approach in hematological disorders, including beta-thalassemia and sickle cell anemia.
Lampronti
Ilaria
I
Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy.
Bianchi
Nicoletta
N
Borgatti
Monica
M
Fibach
Eitan
E
Prus
Eugenia
E
Gambari
Roberto
R
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000378:metabolism; D005319:Fetal Hemoglobin / Q000096:biosynthesis; D011564:Furocoumarins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D005914:Globins / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008926:Plicamycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011564:Furocoumarins; D012333:RNA, Messenger; D003561:Cytarabine; D005914:Globins; D005319:Fetal Hemoglobin; C011659:angelicin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D008926:Plicamycin; D002945:Cisplatin; D006918:Hydroxyurea