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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/79251
Title: Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at <sup>G</sup>γ-globin gene promoter
Authors: Khanita Nuamsee
Thipphawan Chuprajob
Wachirachai Pabuprapap
Pornrutsami Jintaridth
Thongperm Munkongdee
Phatchariya Phannasil
Jim Vadolas
Pornthip Chaichompoo
Apichart Suksamrarn
Saovaros Svasti
Ramkhamhaeng University
Siam University
Monash University
Mahidol University
Hudson Institute of Medical Research
Keywords: Multidisciplinary
Issue Date: 1-Dec-2021
Citation: Scientific Reports. Vol.11, No.1 (2021)
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.
URI: http://repository.li.mahidol.ac.th/dspace/handle/123456789/79251
metadata.dc.identifier.url: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85104595033&origin=inward
ISSN: 20452322
Appears in Collections:Scopus 2021

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