Furocoumarins photolysis products induce differentiation of human erythroid cells.
Psoralens, also known as furocoumarins, are a well-known class of photosensitizers largely used in the therapy of various skin disease. In this study we have evaluated the effects of crude pre-irradiated solutions of furocoumarins derivatives on (a) erythroid differentiation and apoptosis of human leukemic K562 cells and (b) hemoglobin synthesis in cultures of human erythroid progenitors derived from the peripheral blood. To prove the activity of a mixture of photoproducts generated by UVA irradiation of the three psoralen derivatives 5-methoxypsoralen (5-MOP) 8-methoxypsoralen (8-MOP), and angelicin (ANG), we employed the human leukemic K562 cell line and the two-phase liquid culture procedure for growing erythroid progenitors. The results obtained demonstrate that pre-irradiated solutions of psoralen derivatives significantly induce erythroid differentiation of K562 cells irrespective of the type of derivative used, suggesting that the active photoproduct(s) share a common structure. Interestingly, solutions of psoralens irradiated in anaerobic conditions do not exhibits erythroid inducing ability, indicating that the effect is mostly due to photooxidized psoralen products. In erythroid precursor cells, psoralens photolysis products stimulates at low concentrations an increase of hemoglobin A and hemoglobin F. Altogether, these data suggest that photoproducts of psoralen warrant further evaluation as potential therapeutic drugs in beta-thalassaemia and sickle cell anaemia.
Viola
Giampietro
G
Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, University of Padova, 35131 Padova, Italy.
Vedaldi
Daniela
D
Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, University of Padova, 35131 Padova, Italy.
Dall'Acqua
Francesco
F
Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, University of Padova, 35131 Padova, Italy.
Lampronti
Ilaria
I
ER-GenTech, Department of Biochemistry and Molecular Biology, Section of Molecular Biology, University of Ferrara, Ferrara, Italy.
Bianchi
Nicoletta
N
ER-GenTech, Department of Biochemistry and Molecular Biology, Section of Molecular Biology, University of Ferrara, Ferrara, Italy.
Zuccato
Cristina
C
ER-GenTech, Department of Biochemistry and Molecular Biology, Section of Molecular Biology, University of Ferrara, Ferrara, Italy.
Borgatti
Monica
M
ER-GenTech, Department of Biochemistry and Molecular Biology, Section of Molecular Biology, University of Ferrara, Ferrara, Italy.
Gambari
Roberto
R
ER-GenTech, Department of Biochemistry and Molecular Biology, Section of Molecular Biology, University of Ferrara, Ferrara, Italy; GenTech-for-Thal, Laboratory for the Development of Pharmacological and Pharmacogenomic Therapy of Thalassaemia, Biotechnology Centre, Ferrara, Italy.
D000078223:5-Methoxypsoralen; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D041905:Erythroid Cells / Q000187:drug effects* / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects*; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D006454:Hemoglobins / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D008730:Methoxsalen / Q000031:analogs & derivatives / Q000494:pharmacology / Q000528:radiation effects; D010782:Photolysis; D014466:Ultraviolet Rays
D011564:Furocoumarins; D006454:Hemoglobins; D000078223:5-Methoxypsoralen; C011659:angelicin; D008730:Methoxsalen