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Epigenetic and Transcriptional Modulator Potential of Epigallocatechin-3-gallate and Genistein on Fetal Hemoglobin Reactivators Genes

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Clinical Complementary Medicine and Pharmacology 2022年第2期2卷 39-49页

作者： Edna Ribeiro mariana delgadinho Elisabete Matos Raquel Santos Daniela Sousa Heloísa Galante Miguel Britoa H&TRC-Health and Technology Research Center ESTeSL-Escola Superior de Tecnologia da SaúdeInstituto Politécnico de LisboaAv.D.João IILote 4.69.01Parque das NaçõesLisboa 1990-096Portugal Faculty of Sciences of the University of Lisbon Universidade de LisboaCampo Grande 016Lisboa 1749-016Portugal

Background:𝛽-hemoglobinopathies are one of the most common recessive genetic diseases worldwide,with limited treatments available,particularly in developed countries where the prevalence is *** reactivation of Fetal Hemoglobin(HbF)is a promising therapeutic ***,approximately 25%of the patients do not respond to Hydroxyurea(HU),the first and most commonly used HbF inducing agent approved by the ***: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’s in vivo effects in hematological parameters of healthy ***:K562 cells were exposed for 72 and 96 h to GN and EGCG at 100,250 and 500 ng/*** proliferation and viability were measured,and transcriptional levels were evaluated by *** in vivo assay,complete blood count was determined by flow cytometry and HbF level was determined through HPLC in 30 healthy individuals before and after 225 mg EGCG ingestion per day during a 90-day ***:Both compounds impact cellular metabolism and proliferation with no cytotoxic *** GN and EGCG effects in globin and BGLT3 expression levels suggest the involvement of divergent signaling *** for the epigenetic potential,EGCG particularly affects HDAC2 and HDAC8 transcription,whereas GN signifi-cantly affects expression patterns of methylation and acetylation *** appears to have time divergent effects,with 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 ***:Our results advocate EGCG and GN

关键词： Epigenetic modulators Fetal hemoglobin Genistein Epigallocatechin-3-gallate In vitro transcriptional effects In vivo hematologic effects

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