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

2022-06Journal article Open access
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dc.contributor.authorRibeiro, Edna
dc.contributor.authorDelgadinho, Mariana
dc.contributor.authorMatos, Elisabete
dc.contributor.authorSantos, Raquel
dc.contributor.authorSousa, Daniela
dc.contributor.authorGalante, Heloísa
dc.contributor.authorBrito, Miguel
dc.date.accessioned2022-04-22T10:24:35Z
dc.date.available2024-04-22T00:30:20Z
dc.date.issued2022-06
dc.descriptionProjecto IDI&CA - IPL/2019/HemoFet_ESTeSLpt_PT
dc.description.abstractBackground: 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRibeiro 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.pt_PT
dc.identifier.doi10.1016/j.ccmp.2022.100034pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/14584
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationIPL/2019/HemoFet_ESTeSLpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S2772371222000158pt_PT
dc.subjectEpigenetic modulatorspt_PT
dc.subjectFetal hemoglobinpt_PT
dc.subjectGenisteinpt_PT
dc.subjectEpigallocatechin-3-gallatept_PT
dc.subjectIn vitro transcriptional effectspt_PT
dc.subjectIn vivo hematologic effectspt_PT
dc.subjectIPL/2019/HemoFet_ESTeSLpt_PT
dc.titleEpigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue2pt_PT
oaire.citation.startPage100034pt_PT
oaire.citation.titleClinical Complementary Medicine and Pharmacologypt_PT
oaire.citation.volume2pt_PT
person.familyNameRibeiro
person.familyNameBrito
person.givenNameEdna
person.givenNameMiguel
person.identifier.ciencia-idC414-CDF2-D35A
person.identifier.ciencia-id231F-F341-7E93
person.identifier.orcid0000-0003-1316-7750
person.identifier.orcid0000-0001-6394-658X
person.identifier.ridA-7970-2016
person.identifier.scopus-author-id35224551000
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationa571bf34-bcda-49ca-b5cb-4cdecbb3d9c7
relation.isAuthorOfPublication4252d8e0-800c-4d67-8b13-0b711d860669
relation.isAuthorOfPublication.latestForDiscovery4252d8e0-800c-4d67-8b13-0b711d860669

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