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

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-d...

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Autores principales:	Khanita Nuamsee, Thipphawan Chuprajob, Wachirachai Pabuprapap, Pornrutsami Jintaridth, Thongperm Munkongdee, Phatchariya Phannasil, Jim Vadolas, Pornthip Chaichompoo, Apichart Suksamrarn, Saovaros Svasti
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5694a30faffe46378b10206ef2d7f730
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spelling	oai:doaj.org-article:5694a30faffe46378b10206ef2d7f7302021-12-02T18:27:49ZTrienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter10.1038/s41598-021-87738-22045-2322https://doaj.org/article/5694a30faffe46378b10206ef2d7f7302021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87738-2https://doaj.org/toc/2045-2322Abstract 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.Khanita NuamseeThipphawan ChuprajobWachirachai PabuprapapPornrutsami JintaridthThongperm MunkongdeePhatchariya PhannasilJim VadolasPornthip ChaichompooApichart SuksamrarnSaovaros SvastiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Khanita Nuamsee Thipphawan Chuprajob Wachirachai Pabuprapap Pornrutsami Jintaridth Thongperm Munkongdee Phatchariya Phannasil Jim Vadolas Pornthip Chaichompoo Apichart Suksamrarn Saovaros Svasti Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter
description	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.
format	article
author	Khanita Nuamsee Thipphawan Chuprajob Wachirachai Pabuprapap Pornrutsami Jintaridth Thongperm Munkongdee Phatchariya Phannasil Jim Vadolas Pornthip Chaichompoo Apichart Suksamrarn Saovaros Svasti
author_facet	Khanita Nuamsee Thipphawan Chuprajob Wachirachai Pabuprapap Pornrutsami Jintaridth Thongperm Munkongdee Phatchariya Phannasil Jim Vadolas Pornthip Chaichompoo Apichart Suksamrarn Saovaros Svasti
author_sort	Khanita Nuamsee
title	Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter
title_short	Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter
title_full	Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter
title_fullStr	Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter
title_full_unstemmed	Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter
title_sort	trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at gγ-globin gene promoter
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5694a30faffe46378b10206ef2d7f730
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Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter

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