Screening of Curcuminoid Analogs as Potential Hemoglobin F Inducer in K562::Δ^Gγ-^Aγ EGFP Cells

Abstract

Background: β-Thalassemia is a hereditary hematological disease resulting from a defect in β-globin chain production. The reduction or absence β-globin chain production causes an excess of unbound α-globin chains in erythroid progenitors. This leads to pathologies in thalassemia patients, including chronic anemia, iron overload, and other complications. Stimulating γ-globin chain production, which can be assembled with excess unbound α-globin chains to form hemoglobin F (HbF, α2γ2) and compensate for the reduced amount of β-globin synthesis, can ameliorate disease severity. Currently, hydroxyurea (HU) is the only USFDA-approved drug to treat β-hemoglobinopathies. However, only 30-50% of patients respond to HU. Therefore, a novel HbF inducer as an alternative treatment is needed. Method: In this study, we evaluated HbF-inducing properties of 3 curcuminoids derived from Curcuma longa and their 17 analogs in a reporter cell line carrying enhanced green fluorescent protein (EGFP) gene under control of γ-globin promoter, K562::ΔGγ-Aγ EGFP cells. Results: The results showed that curcuminoids and 8 analogs significantly enhanced HbF production with low toxicity. Particularly, compound 16 exhibited the most potent EGFP expression with a 4.4 ± 0.3-fold increase. Conclusion: This study provides the potential of compound 16 to be developed as a new HbF inducer for treatment of β-thalassemia patients.