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

作     者：Edna Ribeiro Mariana Delgadinho Elisabete Matos Raquel Santos Daniela Sousa Heloísa Galante Miguel Britoa 

作者机构：H&TRC-Health and Technology Research CenterESTeSL-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 LisbonUniversidade de LisboaCampo Grande 016Lisboa 1749-016Portugal 

出 版 物：《Clinical Complementary Medicine and Pharmacology》 (临床补充医学和药理学（英文）)

年 卷 期：2022年第2卷第2期

页      面：39-49页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：an IDI&CA grant IPL/2019/HemoFet_ESTeSL and by H&TRC-Health&Technology Re-search Center ESTeSL-Escola Superior de Tecnologia da Saúde Insti-tuto Politécnico de Lisboa 

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

摘      要：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