Increase in gamma-globin mRNA content in human erythroid cells treated with angelicin analogs.
The aim of the present study was to identify molecular analogs of angelicin (ANG) able to increase erythroid differentiation of K562 cells and expression of gamma-globin genes in human erythroid precursor cells, with low effects on apoptosis. ANG-like molecules are well-known photosensitizers largely used for their antiproliferative activity in the treatment of different skin diseases (i.e., psoriasis, vitiligo, eczema, and mycosis fungoides). To verify the activity of these derivatives, we employed three experimental cell systems: (1) the human leukemic K562 cell line, (2) K562 cell clones stably transfected with a pCCL construct carrying green-EGFP under the gamma-globin gene promoter, and (3) the two-phase liquid culture of human erythroid progenitors isolated from normal donors and beta-thalassemia patients. The results of our study suggest that trimethyl ANG is a powerful inducer of erythroid differentiation, compared with known inducers, such as ANG, cytosine arabinoside, mithramycin, and cisplatin. These data could have practical relevance, because pharmacologically mediated regulation of human gamma-globin gene expression, with the consequent induction of fetal hemoglobin, 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, Via Fossato di Mortara, 74, 44100, Ferrara, Italy.
Bianchi
Nicoletta
N
Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44100, Ferrara, Italy.
Zuccato
Cristina
C
Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44100, Ferrara, Italy.
Dall'Acqua
Francesco
F
Department of Pharmaceutical Sciences, University of Padova, Padova, Italy.
Vedaldi
Daniela
D
Department of Pharmaceutical Sciences, University of Padova, Padova, Italy.
Viola
Giampietro
G
Department of Pharmaceutical Sciences, University of Padova, Padova, Italy.
Potenza
Rocco
R
S.I.T. ULSS 18, Rovigo, Servizio di Immunoematologia e Trasfusione, Rovigo, Italy.
Chiavilli
Francesco
F
S.I.T. ULSS 18, Rovigo, Servizio di Immunoematologia e Trasfusione, Rovigo, Italy.
Breveglieri
Giulia
G
Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44100, Ferrara, Italy.
Borgatti
Monica
M
Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44100, Ferrara, Italy.
Finotti
Alessia
A
Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44100, Ferrara, Italy.
Feriotto
Giordana
G
Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44100, Ferrara, Italy.
Salvatori
Francesca
F
Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44100, Ferrara, Italy.
Gambari
Roberto
R
Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44100, Ferrara, Italy. gam@unife.it.
D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D041905:Erythroid Cells / Q000166:cytology / Q000187:drug effects*; D005319:Fetal Hemoglobin / Q000235:genetics; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000473:pathology*; D055545:gamma-Globins / Q000235:genetics*
D011564:Furocoumarins; D012333:RNA, Messenger; D055545:gamma-Globins; D049452:Green Fluorescent Proteins; C021665:4,5'-dimethylangelicin; D005319:Fetal Hemoglobin; C059518:6,5'-dimethylangelicin; C011659:angelicin; C041621:4,4',6-trimethylangelicin