Effects on erythroid differentiation of platinum(II) complexes of synthetic bile acid derivatives.
In this study, we compared some bile acid derivatives and their platinum(II) complexes with respect to their ability to induce erythroid differentiation of human leukemic K562 cells. The complexes analyzed were cis-[(3-dehydrocholanoyliden-L-tartrate)-diammineplatinum(II)] (compound 1) and cis-[di(dehydrocholanoate)-bis(triphenylphosphine)-platinum(II)] (compound 3), together with their free ligands, respectively, 3-dehydrocholanoyliden-L-tartaric acid (compound 2) and dehydrocholanoic acid (4), and their parent compounds, respectively, cisplatin and cis-[dichloride-bis(triphenylphosphine)-platinum(II)] (5). We found that compound 1 stimulates erythroid differentiation of K562 cells and an increase of fetal hemoglobin (HbF) production in erythroid precursor cells isolated from peripheral blood of human subjects. This increase is similar to that obtained by hydroxyurea, a potent inducer of HbF production both in vitro and in vivo. Another important conclusion of this study is related to the evaluation of the effects of compound 1 on production of gamma-globin mRNA in human erythroid precursors grown in the two-stage liquid culture system. We demonstrated that compound 1 induces preferential accumulation of gamma-globin mRNA. The results presented in this manuscript could have practical impact, since it is well known that an increase in HbF production could ameliorate the clinical status of patients with beta-thalassemia and sickle cell anemia.
Lampronti
Ilaria
I
ER-GenTech, Department of Biochemistry and Molecular Biology, Molecular Biology Section, University of Ferrara, Ferrara, Italy.
Bianchi
Nicoletta
N
Zuccato
Cristina
C
Medici
Alessandro
A
Bergamini
Paola
P
Gambari
Roberto
R
D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects*; D005914:Globins / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D013329:Structure-Activity Relationship
D001647:Bile Acids and Salts; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; C513015:cis-((3-dehydrocholanoyliden-L-tartrate)-diammineplatinum(II)); C513016:cis-(di(dehydrocholanoate)-bis(triphenylphosphine)-platinum(II)); D005914:Globins