Treatment of Erythroid Precursor Cells from β-Thalassemia Patients with Cinchona Alkaloids: Induction of Fetal Hemoglobin Production

International Journal of Molecular Sciences

Roberto Gambari¹  Monica Borgatti¹  Lucia Carmela Cosenza¹  Matteo Zurlo¹  Ilaria Lampronti¹  Cristina Zuccato¹  Alessia Finotti¹  Chiara Scapoli² 

[1] Section of Biochemistry and Molecular Biology, Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy;Section of Biology and Evolution, Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy;

关键词: β-thalassemia;    fetal hemoglobin;    γ-globin;    HbF induction;    K562 cells;    Cinchona alkaloids;   

DOI  :  10.3390/ijms222413433

来源: DOAJ

【 摘 要 】

β-thalassemias are among the most common inherited hemoglobinopathies worldwide and are the result of autosomal mutations in the gene encoding β-globin, causing an absence or low-level production of adult hemoglobin (HbA). Induction of fetal hemoglobin (HbF) is considered to be of key importance for the development of therapeutic protocols for β-thalassemia and novel HbF inducers need to be proposed for pre-clinical development. The main purpose on this study was to analyze Cinchona alkaloids (cinchonidine, quinidine and cinchonine) as natural HbF-inducing agents in human erythroid cells. The analytical methods employed were Reverse Transcription quantitative real-time PCR (RT-qPCR) (for quantification of γ-globin mRNA) and High Performance Liquid Chromatography (HPLC) (for analysis of the hemoglobin pattern). After an initial analysis using the K562 cell line as an experimental model system, showing induction of hemoglobin and γ-globin mRNA, we verified whether the two more active compounds, cinchonidine and quinidine, were able to induce HbF in erythroid progenitor cells isolated from β-thalassemia patients. The data obtained demonstrate that cinchonidine and quinidine are potent inducers of γ-globin mRNA and HbF in erythroid progenitor cells isolated from nine β-thalassemia patients. In addition, both compounds were found to synergize with the HbF inducer sirolimus for maximal production of HbF. The data obtained strongly indicate that these compounds deserve consideration in the development of pre-clinical approaches for therapeutic protocols of β-thalassemia.

【 授权许可】

Unknown