Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ globin gene promoter

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Research Article: Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ‑globin gene promoter
Author: Khanita Nuamsee, Thipphawan Chuprajob, Wachirachai Pabuprapap, Pornrutsami Jintaridth, Thongperm Munkongdee, Phatchariya Phannasil, Jim Vadolas, Pornthip Chaichompoo, Apichart Suksamrarn and Saovaros Svasti
Email: thipphawan@siam.edu
Department/Faculty Department of Chemistry, Faculty of Science,  Siam University, Bangkok 10160
Published/แหล่งเผยแพร่ Scientific Reports 2021 VOL.11 NO.8552 (p1-9)

Citation

Khanita Nuamsee, Thipphawan Chuprajob, Wachirachai Pabuprapap, Pornrutsami Jintaridth, Thongperm Munkongdee, Phatchariya Phannasil, Jim Vadolas, Pornthip Chaichompoo, Apichart Suksamrarn and Saovaros Svasti. (2021). Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ‑globin gene promoter. Scientific Reports, 11(8552), 1-9.


ABSTRACT

The reactivation of γ‑globin chain synthesis to combine with excess free α‑globin chains and form fetal hemoglobin (HbF) is an important alternative treatment for β‑thalassemia. We had reported HbF induction property of natural curcuminoids, curcumin (Cur), demethoxycurcumin (DMC) and bis‑demethoxycurcumin (BDMC), in erythroid progenitors. Herein, the HbF induction property of trienone analogs of the three curcuminoids in erythroleukemic K562 cell lines and primary human erythroid progenitor cells from β‑thalassemia/HbE patients was examined. All three trienone analogs could induce HbF synthesis. The most potent HbF inducer in K562 cells was trienone analog of BDMC (T‑BDMC) with 2.4 ± 0.2 fold increase. In addition, DNA methylation at CpG − 53, − 50 and + 6 of Gγ‑globin gene promoter in K562 cells treated with the compounds including T‑BDMC (9.3 ± 1.7%, 7.3 ± 1.7% and 5.3 ± 0.5%, respectively) was significantly lower than those obtained from the control cells (30.7 ± 3.8%, 25.0 ± 2.9% and 7.7 ± 0.9%, respectively P < 0.05). The trienone compounds also significantly induced HbF synthesis in β‑thalassemia/HbE erythroid progenitor cells with significantly reduction in DNA methylation at CpG + 6 of Gγ‑globin gene promoter. These results suggested that the curcuminoids and their three trienone analogs induced HbF synthesis by decreased DNA methylation at Gγ‑globin promoter region, without effect on Aγ‑globin promoter region.


Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ‑globin gene promoter

Faculty of Science, Siam University, Bangkok, Thailand

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