Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes

Detalhes bibliográficos
Autor(a) principal: Ribeiro, Edna
Data de Publicação: 2022
Outros Autores: Delgadinho, Mariana, Matos, Elisabete, Santos, Raquel, Sousa, Daniela, Galante, Heloísa, Brito, Miguel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.21/14584
Resumo: Projecto IDI&CA - IPL/2019/HemoFet_ESTeSL
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spelling Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genesEpigenetic modulatorsFetal hemoglobinGenisteinEpigallocatechin-3-gallateIn vitro transcriptional effectsIn vivo hematologic effectsIPL/2019/HemoFet_ESTeSLProjecto IDI&CA - IPL/2019/HemoFet_ESTeSLBackground: β-hemoglobinopathies is one of the most common recessive genetic diseases worldwide, with limited treatments available, particularly in developed countries where the prevalence is higher. Pharmacological reactivation of Fetal Hemoglobin (HbF) is a promising therapeutic strategy. However, approximately 25% of the patients do not respond to Hydroxyurea (HU), the first and most commonly used HbF inducing agent approved by the FDA. Objective: Here, we performed an in vitro assessment of transcriptional effects induced by natural bioactive compounds, namely Epigallocatechin-3-gallate (EGCG) and Genistein (GN) in globin genes (HBA1, HBB, HBG1, and HBG2) in HbF regulators/silencer genes (KLF1, BCL11A, MYB, and BGLT3) and in epigenetic regulator genes (DNMT1, DNMT3A, DNMT3B, HDAC1, HDAC2, HDAC3, and HDAC8). Moreover, we evaluated EGCG in vivo effects on hematological parameters of healthy volunteers. Methods: K562 cells were exposed for 72 and 96 h to GN and EGCG at 100, 250, and 500 ng/ml. Cell proliferation and viability were measured, and transcriptional levels were evaluated by qRT-PCR. For in vivo assay, complete blood count was determined by flow cytometry and HbF through HPLC in 30 healthy individuals before and after 225 mg EGCG ingestion per day during a 90-day period. Results: Both compounds impact cellular metabolism and proliferation with no cytotoxic effects. Divergent GN and EGCG effects in globin and BGLT3 expression levels suggest the involvement of divergent signaling pathways. As for the epigenetic potential, EGCG particularly affects HDAC2 and HDAC8 transcription, whereas GN significantly affects expression patterns of methylation and acetylation modulators. HU appears to have time divergent effects, with a greater impact in methylation at 72 h (overregulates DNTM3A) while affecting acetylation mostly at 96 h (downregulates HDAC1 and HDAC8). Additionally, in vivo, EGCG demonstrated a modulator effect in hematopoiesis and HbF induction. Conclusion: Our results advocate EGCG and GN with HbF pharmacological reactivation potential and sustain further research as new alternative approaches for β-hemoglobinopathies therapies.ElsevierRCIPLRibeiro, EdnaDelgadinho, MarianaMatos, ElisabeteSantos, RaquelSousa, DanielaGalante, HeloísaBrito, Miguel2022-062022-06-01T00:00:00Z2024-04-22T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.21/14584engRibeiro E, Delgadinho M, Matos E, Santos R, Sousa D, Brito M, et al. Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes. Clin Complement Med Pharmacol. 2022;2(2):100034.10.1016/j.ccmp.2022.100034info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-08-03T10:10:56Zoai:repositorio.ipl.pt:10400.21/14584Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:22:21.879479Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes
title Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes
spellingShingle Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes
Ribeiro, Edna
Epigenetic modulators
Fetal hemoglobin
Genistein
Epigallocatechin-3-gallate
In vitro transcriptional effects
In vivo hematologic effects
IPL/2019/HemoFet_ESTeSL
title_short Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes
title_full Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes
title_fullStr Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes
title_full_unstemmed Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes
title_sort Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes
author Ribeiro, Edna
author_facet Ribeiro, Edna
Delgadinho, Mariana
Matos, Elisabete
Santos, Raquel
Sousa, Daniela
Galante, Heloísa
Brito, Miguel
author_role author
author2 Delgadinho, Mariana
Matos, Elisabete
Santos, Raquel
Sousa, Daniela
Galante, Heloísa
Brito, Miguel
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv RCIPL
dc.contributor.author.fl_str_mv Ribeiro, Edna
Delgadinho, Mariana
Matos, Elisabete
Santos, Raquel
Sousa, Daniela
Galante, Heloísa
Brito, Miguel
dc.subject.por.fl_str_mv Epigenetic modulators
Fetal hemoglobin
Genistein
Epigallocatechin-3-gallate
In vitro transcriptional effects
In vivo hematologic effects
IPL/2019/HemoFet_ESTeSL
topic Epigenetic modulators
Fetal hemoglobin
Genistein
Epigallocatechin-3-gallate
In vitro transcriptional effects
In vivo hematologic effects
IPL/2019/HemoFet_ESTeSL
description Projecto IDI&CA - IPL/2019/HemoFet_ESTeSL
publishDate 2022
dc.date.none.fl_str_mv 2022-06
2022-06-01T00:00:00Z
2024-04-22T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.21/14584
url http://hdl.handle.net/10400.21/14584
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Ribeiro E, Delgadinho M, Matos E, Santos R, Sousa D, Brito M, et al. Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genes. Clin Complement Med Pharmacol. 2022;2(2):100034.
10.1016/j.ccmp.2022.100034
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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