Skip to content
2000
Volume 4, Issue 1
  • ISSN: 2666-2906
  • E-ISSN: 2666-2914

Abstract

Despite enormous advances in the current treatment strategies, liver diseases are associated with high mortality. It is critical to discover novel drug targets for developing effective therapies. Histone deacetylase (HDAC) inhibitors have emerged as a promising therapeutic approach for the treatment of various liver diseases. The use of histone deacetylases and their inhibitors to treat a variety of liver illnesses has been thoroughly reviewed using suitable keywords and key phrases as search terms within scientific databases like Web of Science, Google Scholar, PubMed, and other web sources, and data was collected and sorted from the literature spanning from 1990 to 2023, providing an overview of the role of HDACs in liver diseases together with the evidence of the therapeutic effects of HDAC inhibitors in various liver diseases. HDACs are enzymes that play a crucial role in regulating gene expression by deacetylating histone proteins, which can alter chromatin structure and thereby regulate gene expression. Dysregulation of HDAC activity is associated with liver diseases, including Hepatocellular carcinoma (HCC), non-alcoholic fatty liver disease (NAFLD), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections, . as implicated in many studies both and . This review summarizes the prevalence of liver diseases and how their impact is significant. We highlight the crucial role of histone deacetylases (HDACs) in liver diseases. In addition, by targeting various mechanisms, HDAC inhibitors have shown promise as novel hepatoprotective agents. These inhibitors can have therapeutic effects in different liver diseases. They can induce cell cycle arrest, promote apoptosis, improve insulin resistance, address hepatic steatosis, and enhance differentiation in hepatocellular carcinoma (HCC) cells. The multifaceted approach of HDAC inhibitors offers potential for innovative treatments in liver diseases.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ijghd/10.2174/0126662906313034241223071431
2025-01-28
2025-09-26

  • From This Site

    /content/journals/ijghd/10.2174/0126662906313034241223071431
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. KalraA. YetiskulE. WehrleC.J. Physiology, LiverStatPearls Publishing2023
     [Google Scholar]
  2. CheemerlaS. BalakrishnanM. Global epidemiology of chronic liver disease.Clin. Liver Dis.202117536537010.1002/cld.106134136143
     [Google Scholar]
  3. SepanlouS.G. SafiriS. BisignanoC. IkutaK.S. MeratS. SaberifirooziM. PoustchiH. TsoiD. ColombaraD.V. AbdoliA. AdedoyinR.A. AfaridehM. AgrawalS. AhmadS. AhmadianE. AhmadpourE. AkinyemijuT. AkunnaC.J. AlipourV. Almasi-HashianiA. AlmulhimA.M. Al-RaddadiR.M. Alvis-GuzmanN. AnberN.H. AngusC. AnoushiravaniA. ArablooJ. ArayaE.M. AsmelashD. AtaeiniaB. AtaroZ. AtoutM.M.W. AusloosF. AwasthiA. BadawiA. BanachM. Bejarano RamirezD.F. BhagavathulaA.S. BhalaN. BhattacharyyaK. BiondiA. BollaS.R. BoloorA. BorzìA.M. ButtZ.A. CámeraL.L.A.A. Campos-NonatoI.R. CarvalhoF. ChuD-T. ChungS-C. CortesiP.A. CostaV.M. CowieB.C. DaryaniA. de CourtenB. DemozG.T. DesaiR. DharmaratneS.D. DjalaliniaS. DoH.T. DorostkarF. DrakeT.M. DubeyM. DuncanB.B. EffiongA. EftekhariA. ElsharkawyA. EtemadiA. FarahmandM. FarzadfarF. FernandesE. FilipI. FischerF. GebremedhinK.B.B. GetaB. GilaniS.A. GillP.S. GutirrezR.A. HaileM.T. Haj-MirzaianA. HamidS.S. HasankhaniM. HasanzadehA. HashemianM. HassenH.Y. HayS.I. HayatK. HeidariB. HenokA. HoangC.L. HostiucM. HostiucS. HsiehV.C. IgumborE.U. IlesanmiO.S. IrvaniS.S.N. Jafari BalalamiN. JamesS.L. JeemonP. JhaR.P. JonasJ.B. JozwiakJ.J. KabirA. KasaeianA. KassayeH.G. KefaleA.T. KhalilovR. KhanM.A. KhanE.A. KhaterA. KimY.J. KoyanagiA. La VecchiaC. LimL-L. LopezA.D. LorkowskiS. LotufoP.A. LozanoR. Magdy Abd El RazekM. MaiH.T. ManafiN. ManafiA. MansourniaM.A. MantovaniL.G. MazzagliaG. MehtaD. MendozaW. MenezesR.G. MengeshaM.M. MeretojaT.J. MestrovicT. MiazgowskiB. MillerT.R. MirrakhimovE.M. MithraP. MoazenB. MoghadaszadehM. Mohammadian-HafshejaniA. MohammedS. MokdadA.H. Montero-ZamoraP.A. MoradiG. NaimzadaM.D. NayakV. NegoiI. NguyenT.H. Ofori-AsensoR. OhI-H. OlagunjuT.O. PadubidriJ.R. PakshirK. PanaA. PathakM. PourshamsA. RabieeN. RadfarA. RafieiA. RamezanzadehK. RanaS.M.M. RawafS. RawafD.L. ReinerR.C.Jr RoeverL. RoomR. RoshandelG. SafariS. SamyA.M. SanabriaJ. SartoriusB. SchmidtM.I. SenthilkumaranS. ShaikhM.A. SharifM. SharifiA. ShigematsuM. SinghJ.A. SoheiliA. SuleriaH.A.R. TeklehaimanotB.F. TesfayB.E. VacanteM. Vahedian-AzimiA. ValdezP.R. VasankariT.J. VuG.T. WaheedY. WeldegwergsK.G. WerdeckerA. WestermanR. WondafrashD.Z. WondmienehA.B. YeshitilaY.G. YonemotoN. YuC. ZaidiZ. ZarghiA. Zelber-SagiS. ZewdieK.A. ZhangZ-J. ZhaoX-J. NaghaviM. MalekzadehR. GBD 2017 Cirrhosis Collaborators The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol. Hepatol.20205324526610.1016/S2468‑1253(19)30349‑831981519
     [Google Scholar]
  4. MokdadA.A. LopezA.D. ShahrazS. LozanoR. MokdadA.H. StanawayJ. MurrayC.J.L. NaghaviM. Liver cirrhosis mortality in 187 countries between 1980 and 2010: A systematic analysis.BMC Med.201412114510.1186/s12916‑014‑0145‑y25242656
     [Google Scholar]
  5. SinghR. KumarS. RanaA.C. SharmaN. Different models of hepatotoxicity and related liver diseases: A review.IRJP2012378695
     [Google Scholar]
  6. SwaroopT.V.S.S. GowdaK.P.S. Hepatotoxicity mechanisms and its biomarkers.IJPCS201212675682
     [Google Scholar]
  7. SaimanY. FriedmanS.L. The role of chemokines in acute liver injury.Front. Physiol.2012321310.3389/fphys.2012.0021322723782
     [Google Scholar]
  8. Cichoż-LachH. MichalakA. Oxidative stress as a crucial factor in liver diseases.World J. Gastroenterol.201420258082809110.3748/wjg.v20.i25.808225009380
     [Google Scholar]
  9. Garcia-LezanaT. Lopez-CanovasJ.L. VillanuevaA. Signaling pathways in hepatocellular carcinoma.Adv. Cancer Res.20211496310110.1016/bs.acr.2020.10.00233579428
     [Google Scholar]
  10. SetoE YoshidaM Erasers of histone acetylation: The histone deacetylase enzymes.Cold Spring Harb. Perspect. Biol.20146410.1101/cshperspect.a018713
     [Google Scholar]
  11. TakW.Y. RyooB.Y. LimH.Y. KimD.Y. OkusakaT. IkedaM. HidakaH. YeonJ.E. MizukoshiE. MorimotoM. LeeM.A. YasuiK. KawaguchiY. HeoJ. MoritaS. KimT.Y. FuruseJ. KatayamaK. AramakiT. HaraR. KimuraT. NakamuraO. KudoM. Phase I/II study of first-line combination therapy with sorafenib plus resminostat, an oral HDAC inhibitor, versus sorafenib monotherapy for advanced hepatocellular carcinoma in east Asian patients.Invest. New Drugs20183661072108410.1007/s10637‑018‑0658‑x30198057
     [Google Scholar]
  12. YeoW. ChungH.C. ChanS.L. WangL.Z. LimR. PicusJ. BoyerM. MoF.K.F. KohJ. RhaS.Y. HuiE.P. JeungH.C. RohJ.K. YuS.C.H. ToK.F. TaoQ. MaB.B. ChanA.W.H. TongJ.H.M. ErlichmanC. ChanA.T.C. GohB.C. Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: A multicenter phase I/II study with biomarker and pharmacokinetic analysis of tumors from patients in the mayo phase II consortium and the cancer therapeutics research group.J. Clin. Oncol.201230273361336710.1200/JCO.2011.41.239522915658
     [Google Scholar]
  13. HardyT. MannD.A. Epigenetics in liver disease: From biology to therapeutics.Gut201665111895190510.1136/gutjnl‑2015‑31129227624887
     [Google Scholar]
  14. LiY. SetoE. HDACs and HDAC inhibitors in cancer development and therapy.Cold Spring Harb. Perspect. Med.2016610a02683110.1101/cshperspect.a02683127599530
     [Google Scholar]
  15. MaudeH. Sanchez-CabanillasC. CebolaI. Epigenetics of hepatic insulin resistance.Front. Endocrinol.20211268135610.3389/fendo.2021.68135634046015
     [Google Scholar]
  16. FelkerB.L. SloanK.L. DominitzJ.A. BarnesR.F. The safety of valproic acid use for patients with hepatitis C infection.Am. J. Psychiatry2003160117417810.1176/appi.ajp.160.1.17412505820
     [Google Scholar]
  17. GahrS. WissniowskiT. ZopfS. StrobelD. PustowkaA. OckerM. Combination of the deacetylase inhibitor panobinostat and the multi-kinase inhibitor sorafenib for the treatment of metastatic hepatocellular carcinoma - Review of the underlying molecular mechanisms and first case report.J. Cancer2012315816510.7150/jca.421122514558
     [Google Scholar]
  18. Global hepatitis report.2017Available from: https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/
  19. BlachS. ZeuzemS. MannsM. AltraifI. DubergA-S. MuljonoD.H. WakedI. AlavianS.M. LeeM-H. NegroF. AbaalkhailF. AbdouA. AbdullaM. RachedA.A. AhoI. AkarcaU. Al GhazzawiI. Al KaabiS. Al LawatiF. Al NamaaniK. Al SerkalY. Al-BusafiS.A. Al-DabalL. AlemanS. AlghamdiA.S. AljumahA.A. Al-RomaihiH.E. AnderssonM.I. ArendtV. ArkkilaP. AssiriA.M. BaatarkhuuO. BaneA. Ben-AriZ. BerginC. BessoneF. BihlF. BizriA.R. BlachierM. BlascoA.J. MelloC.E.B. BruggmannP. BruntonC.R. CalinasF. ChanH.L.Y. ChaudhryA. CheinquerH. ChenC-J. ChienR-N. ChoiM.S. ChristensenP.B. ChuangW-L. ChulanovV. CisnerosL. ClausenM.R. CrampM.E. CraxiA. CroesE.A. DalgardO. DaruichJ.R. de LedinghenV. DoreG.J. El-SayedM.H. ErgörG. EsmatG. EstesC. FalconerK. FaragE. FerrazM.L.G. FerreiraP.R. FlisiakR. FrankovaS. GamkrelidzeI. GaneE. García-SamaniegoJ. KhanA.G. GountasI. GoldisA. GottfredssonM. GrebelyJ. GschwantlerM. PessôaM.G. GunterJ. HajarizadehB. HajelssedigO. HamidS. HamoudiW. HatzakisA. HimattS.M. HoferH. HrsticI. HuiY-T. HunyadyB. IdilmanR. JafriW. JahisR. JanjuaN.Z. JarčuškaP. JerumaA. JonassonJ.G. KamelY. KaoJ-H. KaymakogluS. KershenobichD. KhamisJ. KimY.S. KondiliL. KoutoubiZ. KrajdenM. KrarupH. LaiM. LalemanW. LaoW. LavanchyD. LázaroP. LeleuH. LesiO. LesmanaL.A. LiM. LiakinaV. LimY-S. LuksicB. MahomedA. MaimetsM. MakaraM. MaluA.O. MarinhoR.T. MarottaP. MaussS. MemonM.S. CorreaM.C.M. Mendez-SanchezN. MeratS. MetwallyA.M. MohamedR. MorenoC. MouradF.H. MüllhauptB. MurphyK. NdeH. NjouomR. NonkovicD. NorrisS. ObekpaS. OgucheS. OlafssonS. OltmanM. OmedeO. OmuemuC. Opare-SemO. ØvrehusA.L.H. Owusu-OforiS. OyunsurenT.S. PapatheodoridisG. PasiniK. PeltekianK.M. PhillipsR.O. PimenovN. PoustchiH. Prabdial-SingN. QureshiH. RamjiA. Razavi-ShearerD. Razavi-ShearerK. RedaeB. ReesinkH.W. RidruejoE. RobbinsS. RobertsL.R. RobertsS.K. RosenbergW.M. Roudot-ThoravalF. RyderS.D. SafadiR. SagalovaO. SalupereR. SanaiF.M. AvilaJ.F.S. SaraswatV. Sarmento-CastroR. SarrazinC. SchmelzerJ.D. SchréterI. Seguin-DevauxC. ShahS.R. ShararaA.I. SharmaM. ShevaldinA. ShihaG.E. SievertW. SonderupM. SouliotisK. SpeicieneD. SperlJ. StärkelP. StauberR.E. StedmanC. StruckD. SuT-H. SypsaV. TanS-S. TanakaJ. ThompsonA.J. TolmaneI. TomasiewiczK. ValantinasJ. Van DammeP. van der MeerA.J. van ThielI. Van VlierbergheH. VinceA. VogelW. WedemeyerH. WeisN. WongV.W.S. YaghiC. YosryA. YuenM. YunihastutiE. YusufA. ZuckermanE. RazaviH. Polaris Observatory HCV Collaborators Global prevalence and genotype distribution of hepatitis C virus infection in 2015: A modelling study.Lancet Gastroenterol. Hepatol.20172316117610.1016/S2468‑1253(16)30181‑928404132
     [Google Scholar]
  20. SteinE. Cruz-LeminiM. AltamiranoJ. NduggaN. CouperD. AbraldesJ.G. BatallerR. Heavy daily alcohol intake at the population level predicts the weight of alcohol in cirrhosis burden worldwide.J. Hepatol.2016655998100510.1016/j.jhep.2016.06.01827392424
     [Google Scholar]
  21. YounossiZ.M. KoenigA.B. AbdelatifD. FazelY. HenryL. WymerM. Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes.Hepatology2016641738410.1002/hep.2843126707365
     [Google Scholar]
  22. EkstedtM. FranzénL.E. MathiesenU.L. ThoreliusL. HolmqvistM. BodemarG. KechagiasS. Long‐term follow‐up of patients with NAFLD and elevated liver enzymes†.Hepatology200644486587310.1002/hep.2132717006923
     [Google Scholar]
  23. EstesC. RazaviH. LoombaR. YounossiZ. SanyalA.J. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease.Hepatology201867112313310.1002/hep.2946628802062
     [Google Scholar]
  24. MukherjeeP.S. VishnubhatlaS. AmarapurkarD.N. DasK. SoodA. ChawlaY.K. EapenC.E. BodduP. ThomasV. VarshneyS. HidangmayumD.S. BhaumikP. ThakurB. AcharyaS.K. ChowdhuryA. Etiology and mode of presentation of chronic liver diseases in India: A multi centric study.PLoS One20171210e018703310.1371/journal.pone.018703329073197
     [Google Scholar]
  25. MondalD. DasK. ChowdhuryA. Epidemiology of liver diseases in India.Clin. Liver Dis.202219311411710.1002/cld.117735355840
     [Google Scholar]
  26. Hin TangJ.J. Hao ThngD.K. LimJ.J. TohT.B. JAK/STAT signaling in hepatocellular carcinoma.Hepat. Oncol.202071HEP1810.2217/hep‑2020‑000132273976
     [Google Scholar]
  27. RenZ. ChenS. QingT. XuanJ. CouchL. YuD. NingB. ShiL. GuoL. Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells.Toxicology2017392112110.1016/j.tox.2017.10.00228988120
     [Google Scholar]
  28. TianL.Y. SmitD.J. JückerM. The role of PI3K/AKT/mTOR signaling in hepatocellular carcinoma metabolism.Int. J. Mol. Sci.2023243265210.3390/ijms2403265236768977
     [Google Scholar]
  29. LueddeT. SchwabeR.F. NF-κB in the liver—linking injury, fibrosis and hepatocellular carcinoma.Nat. Rev. Gastroenterol. Hepatol.20118210811810.1038/nrgastro.2010.21321293511
     [Google Scholar]
  30. ZhaoS. JiangJ. JingY. LiuW. YangX. HouX. GaoL. WeiL. The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity.Cell Death Dis.20201117010.1038/s41419‑020‑2264‑z31988281
     [Google Scholar]
  31. WangY. NakajimaT. GonzalezF.J. TanakaN. PPARs as metabolic regulators in the liver: Lessons from liver-specific PPAR-null mice.Int. J. Mol. Sci.2020216206110.3390/ijms2106206132192216
     [Google Scholar]
  32. LiQ. SunM. WangM. FengM. YangF. LiL. ZhaoJ. ChangC. DongH. XieT. ChenJ. Dysregulation of Wnt/β‐catenin signaling by protein kinases in hepatocellular carcinoma and its therapeutic application.Cancer Sci.202111251695170610.1111/cas.1486133605517
     [Google Scholar]
  33. KiziltasS. Toll-like receptors in pathophysiology of liver diseases.World J. Hepatol.20168321354136910.4254/wjh.v8.i32.135427917262
     [Google Scholar]
  34. HercegZ. PaliwalA. Epigenetic mechanisms in hepatocellular carcinoma: How environmental factors influence the epigenome.Mutat. Res. Rev. Mutat. Res.20117273556110.1016/j.mrrev.2011.04.00121514401
     [Google Scholar]
  35. BannisterA.J. KouzaridesT. Regulation of chromatin by histone modifications.Cell Res.201121338139510.1038/cr.2011.2221321607
     [Google Scholar]
  36. SpangeS. WagnerT. HeinzelT. KrämerO.H. Acetylation of non-histone proteins modulates cellular signalling at multiple levels.Int. J. Biochem. Cell Biol.200941118519810.1016/j.biocel.2008.08.02718804549
     [Google Scholar]
  37. ChoudharyC. KumarC. GnadF. NielsenM.L. RehmanM. WaltherT.C. OlsenJ.V. MannM. Lysine acetylation targets protein complexes and co-regulates major cellular functions.Science2009325594283484010.1126/science.117537119608861
     [Google Scholar]
  38. KhanN. JeffersM. KumarS. HackettC. BoldogF. KhramtsovN. QianX. MillsE. BerghsS.C. CareyN. FinnP.W. CollinsL.S. TumberA. RitchieJ.W. JensenP.B. LichensteinH.S. SehestedM. Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors.Biochem. J.2008409258158910.1042/BJ2007077917868033
     [Google Scholar]
  39. RuijterA.J.M. GennipA.H. CaronH.N. KempS. KuilenburgA.B.P. Histone deacetylases (HDACs): Characterization of the classical HDAC family.Biochem. J.2003370373774910.1042/bj2002132112429021
     [Google Scholar]
  40. ChenH.P. ZhaoY.T. ZhaoT.C. Histone deacetylases and mechanisms of regulation of gene expression.Crit. Rev. Oncog.2015201-2354710.1615/CritRevOncog.201501299725746103
     [Google Scholar]
  41. HallowsW.C. LeeS. DenuJ.M. Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases.Proc. Natl. Acad. Sci. USA200610327102301023510.1073/pnas.060439210316790548
     [Google Scholar]
  42. LaiI.L. LinT.P. YaoY.L. LinC.Y. HsiehM.J. YangW.M. Histone deacetylase 10 relieves repression on the melanogenic program by maintaining the deacetylation status of repressors.J. Biol. Chem.2010285107187719610.1074/jbc.M109.06186120032463
     [Google Scholar]
  43. ChoY. CavalliV. HDAC signaling in neuronal development and axon regeneration.Curr. Opin. Neurobiol.20142711812610.1016/j.conb.2014.03.00824727244
     [Google Scholar]
  44. Ageta-IshiharaN. MiyataT. OhshimaC. WatanabeM. SatoY. HamamuraY. HigashiyamaT. MazitschekR. BitoH. KinoshitaM. Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation.Nat. Commun.201341253210.1038/ncomms353224113571
     [Google Scholar]
  45. PandithageR. LilischkisR. HartingK. WolfA. JedamzikB. Lüscher-FirzlaffJ. VervoortsJ. LasonderE. KremmerE. KnöllB. LüscherB. The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility.J. Cell Biol.2008180591592910.1083/jcb.20070712618332217
     [Google Scholar]
  46. TianH. LiuS. RenJ. LeeJ.K.W. WangR. ChenP. Role of histone deacetylases in skeletal muscle physiology and systemic energy homeostasis: Implications for metabolic diseases and therapy.Front. Physiol.20201194910.3389/fphys.2020.0094932848876
     [Google Scholar]
  47. ChoiM.C. RyuS. HaoR. WangB. KapurM. FanC.M. YaoT.P. HDAC 4 promotes P ax7‐dependent satellite cell activation and muscle regeneration.EMBO Rep.201415111175118310.15252/embr.20143919525205686
     [Google Scholar]
  48. HullE.E. MontgomeryM.R. LeyvaK.J. HDAC inhibitors as epigenetic regulators of the immune system: Impacts on cancer therapy and inflammatory diseases.BioMed Res. Int.2016201611510.1155/2016/879720627556043
     [Google Scholar]
  49. LicciardiP.V. KaragiannisT.C. Regulation of immune responses by histone deacetylase inhibitors.ISRN Hematol.2012201211010.5402/2012/69090122461998
     [Google Scholar]
  50. FanF. LiuP. BaoR. ChenJ. ZhouM. MoZ. MaY. LiuH. ZhouY. CaiX. QianC. LiuX. A dual PI3K/HDAC inhibitor induces immunogenic ferroptosis to potentiate cancer immune checkpoint therapy.Cancer Res.202181246233624510.1158/0008‑5472.CAN‑21‑154734711611
     [Google Scholar]
  51. BaiX. WuL. LiangT. LiuZ. LiJ. LiD. XieH. YinS. YuJ. LinQ. ZhengS. Overexpression of myocyte enhancer factor 2 and histone hyperacetylation in hepatocellular carcinoma.J. Cancer Res. Clin. Oncol.20071341839110.1007/s00432‑007‑0252‑717611778
     [Google Scholar]
  52. LuX.F. CaoX.Y. ZhuY.J. WuZ.R. ZhuangX. ShaoM.Y. XuQ. ZhouY.J. JiH.J. LuQ.R. ShiY.J. ZengY. BuH. Histone deacetylase 3 promotes liver regeneration and liver cancer cells proliferation through signal transducer and activator of transcription 3 signaling pathway.Cell Death Dis.20189339810.1038/s41419‑018‑0428‑x29540666
     [Google Scholar]
  53. TianY. WongV.W.S. WongG.L.H. YangW. SunH. ShenJ. TongJ.H.M. GoM.Y.Y. CheungY.S. LaiP.B.S. ZhouM. XuG. HuangT.H.M. YuJ. ToK.F. ChengA.S.L. ChanH.L.Y. Histone deacetylase HDAC8 promotes insulin resistance and β-catenin activation in NAFLD associated hepatocellular carcinoma.Cancer Res.201575224803481610.1158/0008‑5472.CAN‑14‑378626383163
     [Google Scholar]
  54. MannaertsI. EysackersN. OnyemaO.O. Van BenedenK. ValenteS. MaiA. OdenthalM. van GrunsvenL.A. Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.PLoS One201381e5578610.1371/journal.pone.005578623383282
     [Google Scholar]
  55. LiX. WuX.Q. XuT. LiX.F. YangY. LiW.X. HuangC. MengX.M. LiJ. Role of histone deacetylases(HDACs) in progression and reversal of liver fibrosis.Toxicol. Appl. Pharmacol.2016306586810.1016/j.taap.2016.07.00327396813
     [Google Scholar]
  56. QinL. HanY.P. Epigenetic repression of matrix metalloproteinases in myofibroblastic hepatic stellate cells through histone deacetylases 4: Implication in tissue fibrosis.Am. J. Pathol.201017741915192810.2353/ajpath.2010.10001120847282
     [Google Scholar]
  57. LeeC.H. ChoiY. ChoH. BangI.H. HaoL. LeeS.O. JeonR. BaeE.J. ParkB.H. Histone deacetylase 8 inhibition alleviates cholestatic liver injury and fibrosis.Biochem. Pharmacol.202118311431210.1016/j.bcp.2020.11431233130126
     [Google Scholar]
  58. GuiseA. BudayevaH. DinerB. CristeaI. Histone deacetylases in herpesvirus replication and virus-stimulated host defense.Viruses2013571607163210.3390/v507160723807710
     [Google Scholar]
  59. LuY. StuartJ.H. Talbot-CooperC. Agrawal-SinghS. HuntlyB. SmidA.I. SnowdenJ.S. DupontL. SmithG.L. Histone deacetylase 4 promotes type I interferon signaling, restricts DNA viruses, and is degraded via vaccinia virus protein C6.Proc. Natl. Acad. Sci. USA201911624119971200610.1073/pnas.181639911631127039
     [Google Scholar]
  60. LiuF. CampagnaM. QiY. ZhaoX. GuoF. XuC. LiS. LiW. BlockT.M. ChangJ. GuoJ.T. Alpha-interferon suppresses hepadnavirus transcription by altering epigenetic modification of cccDNA minichromosomes.PLoS Pathog.201399e100361310.1371/journal.ppat.100361324068929
     [Google Scholar]
  61. YangQ. TangJ. PeiR. GaoX. GuoJ. XuC. WangY. WangQ. WuC. ZhouY. HuX. ZhaoH. WangY. ChenX. ChenJ. Host HDAC4 regulates the antiviral response by inhibiting the phosphorylation of IRF3.J. Mol. Cell Biol.201911215816910.1093/jmcb/mjy03529800227
     [Google Scholar]
  62. AgudeloM. FigueroaG. PariraT. YndartA. MuñozK. AtluriV. SamikkannuT. NairM.P. Profile of class I histone deacetylases (HDAC) by human dendritic cells after alcohol consumption and in vitro alcohol treatment and their implication in oxidative stress: Role of HDAC inhibitors trichostatin A and mocetinostat.PLoS One2016116e015642110.1371/journal.pone.015642127249803
     [Google Scholar]
  63. SeitzHK BatallerR Cortez-PintoH GaoB GualA LacknerC MathurinP MuellerS SzaboG TsukamotoH Alcoholic liver disease.Nat. Rev. Dis. Primers20184112210.1038/s41572‑018‑0014‑7
     [Google Scholar]
  64. TianY. MokM. YangP. ChengA. Epigenetic activation of Wnt/β-catenin signaling in NAFLD-associated hepatocarcinogenesis.Cancers2016887610.3390/cancers808007627556491
     [Google Scholar]
  65. XieH.J. NohJ.H. KimJ.K. JungK.H. EunJ.W. BaeH.J. KimM.G. ChangY.G. LeeJ.Y. ParkH. NamS.W. HDAC1 inactivation induces mitotic defect and caspase-independent autophagic cell death in liver cancer.PLoS One201274e3426510.1371/journal.pone.003426522496786
     [Google Scholar]
  66. BuurmanR. GürlevikE. SchäfferV. EilersM. SandbotheM. KreipeH. WilkensL. SchlegelbergerB. KühnelF. SkawranB. Histone deacetylases activate hepatocyte growth factor signaling by repressing microRNA-449 in hepatocellular carcinoma cells.Gastroenterology20121433811820.e1510.1053/j.gastro.2012.05.03322641068
     [Google Scholar]
  67. YangY. BaeM. ParkY.K. LeeY. PhamT.X. RudraiahS. ManautouJ. KooS.I. LeeJ.Y. Histone deacetylase 9 plays a role in the antifibrogenic effect of astaxanthin in hepatic stellate cells.J. Nutr. Biochem.20174017217710.1016/j.jnutbio.2016.11.00327915160
     [Google Scholar]
  68. TahaT.Y. AnirudhanV. LimothaiU. LoebD.D. PetukhovP.A. McLachlanA. Modulation of hepatitis B virus pregenomic RNA stability and splicing by histone deacetylase 5 enhances viral biosynthesis.PLoS Pathog.2020168e100880210.1371/journal.ppat.100880232822428
     [Google Scholar]
  69. WangY. WangK. FuJ. HDAC6 Mediates Poly (I:C)-Induced TBK1 and Akt Phosphorylation in Macrophages.Front. Immunol.202011177610.3389/fimmu.2020.0177632849638
     [Google Scholar]
  70. KangH. ParkY.K. LeeJ.Y. Inhibition of alcohol-induced inflammation and oxidative stress by astaxanthin is mediated by its opposite actions in the regulation of sirtuin 1 and histone deacetylase 4 in macrophages.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20211866115883810.1016/j.bbalip.2020.15883833065288
     [Google Scholar]
  71. GriffinE.A.Jr MelasP.A. ZhouR. LiY. MercadoP. KempadooK.A. StephensonS. ColnaghiL. TaylorK. HuM.C. KandelE.R. KandelD.B. Prior alcohol use enhances vulnerability to compulsive cocaine self-administration by promoting degradation of HDAC4 and HDAC5.Sci. Adv.2017311e170168210.1126/sciadv.170168229109977
     [Google Scholar]
  72. NiH.M. ChaoX. DingW.X. S100A11 Overexpression Promotes Fatty Liver Diseases via Increased Autophagy?Cell. Mol. Gastroenterol. Hepatol.202111388588610.1016/j.jcmgh.2020.11.01333290740
     [Google Scholar]
  73. JiaH.Y. LiQ.Z. LvL.F. HDAC5 Inhibits Hepatic Lipogenic Genes Expression by Attenuating the Transcriptional Activity of Liver X Receptor.Cell. Physiol. Biochem.20163941561156710.1159/00044785827614433
     [Google Scholar]
  74. ZhangL. ZhangZ. LiC. ZhuT. GaoJ. ZhouH. ZhengY. ChangQ. WangM. WuJ. RanL. WuY. MiaoH. ZouX. LiangB. S100A11 Promotes Liver Steatosis via FOXO1-Mediated Autophagy and Lipogenesis.Cell. Mol. Gastroenterol. Hepatol.202111369772410.1016/j.jcmgh.2020.10.00633075563
     [Google Scholar]
  75. WangZ. WangH. ShenP. XieR. Expression of HDAC4 in Stage B Hepatocellular Carcinoma and Its Influence on Survival.Ann. Clin. Lab. Sci.201949218919231028063
     [Google Scholar]
  76. GuH. FangZ. CaiX. SongR. LinM. YeJ. DingX. KeQ. ChenH. GongC. YeM. Highly expressed histone deacetylase 5 promotes the growth of hepatocellular carcinoma cells by inhibiting the TAp63-maspin pathway.Am. J. Cancer Res.20188346247529637001
     [Google Scholar]
  77. YanX. TianR. SunJ. ZhaoY. LiuB. SuJ. LiM. SunW. XuX. Sorafenib-Induced Autophagy Promotes Glycolysis by Upregulating the p62/HDAC6/HSP90 Axis in Hepatocellular Carcinoma Cells.Front. Pharmacol.20221278866710.3389/fphar.2021.78866735250553
     [Google Scholar]
  78. FanJ. LouB. ChenW. ZhangJ. LinS. LvF. ChenY. Down-regulation of HDAC5 inhibits growth of human hepatocellular carcinoma by induction of apoptosis and cell cycle arrest.Tumour Biol.20143511115231153210.1007/s13277‑014‑2358‑225129440
     [Google Scholar]
  79. FengG.W. DongL.D. ShangW.J. PangX.L. LiJ.F. LiuL. WangY. HDAC5 promotes cell proliferation in human hepatocellular carcinoma by up-regulating Six1 expression.Eur. Rev. Med. Pharmacol. Sci.201418681181624706304
     [Google Scholar]
  80. SatohA. SteinL. ImaiS. The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity.Handb. Exp. Pharmacol.201120612516210.1007/978‑3‑642‑21631‑2_721879449
     [Google Scholar]
  81. HoutkooperR.H. PirinenE. AuwerxJ. Sirtuins as regulators of metabolism and healthspan.Nat. Rev. Mol. Cell Biol.201213422523810.1038/nrm329322395773
     [Google Scholar]
  82. JiangR. ZhouY. WangS. PangN. HuangY. YeM. WanT. QiuY. PeiL. JiangX. HuangY. YangH. LingW. LiX. ZhangZ. YangL. Nicotinamide riboside protects against liver fibrosis induced by CCl4 via regulating the acetylation of Smads signaling pathway.Life Sci.2019225202810.1016/j.lfs.2019.03.06430928408
     [Google Scholar]
  83. WuY. LiuX. ZhouQ. HuangC. MengX. XuF. LiJ. Silent information regulator 1 (SIRT1) ameliorates liver fibrosis via promoting activated stellate cell apoptosis and reversion.Toxicol. Appl. Pharmacol.2015289216317610.1016/j.taap.2015.09.02826435214
     [Google Scholar]
  84. SunL. FanZ. ChenJ. TianW. LiM. XuH. WuX. ShaoJ. BianY. FangM. XuY. Transcriptional repression of SIRT1 by protein inhibitor of activated STAT 4 (PIAS4) in hepatic stellate cells contributes to liver fibrosis.Sci. Rep.2016612843210.1038/srep2843227323886
     [Google Scholar]
  85. KoyamaY. BrennerD.A. Liver inflammation and fibrosis.J. Clin. Invest.20171271556410.1172/JCI8888128045404
     [Google Scholar]
  86. ZhangP. TuB. WangH. CaoZ. TangM. ZhangC. GuB. LiZ. WangL. YangY. ZhaoY. WangH. LuoJ. DengC.X. GaoB. RoederR.G. ZhuW.G. Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion.Proc. Natl. Acad. Sci. USA201411129106841068910.1073/pnas.141102611125009184
     [Google Scholar]
  87. WuT. LiuY.H. FuY.C. LiuX.M. ZhouX.H. Direct evidence of sirtuin downregulation in the liver of non-alcoholic fatty liver disease patients.Ann. Clin. Lab. Sci.201444441041825361925
     [Google Scholar]
  88. YoshizakiT. SchenkS. ImamuraT. BabendureJ.L. SonodaN. BaeE.J. OhD.Y. LuM. MilneJ.C. WestphalC. BandyopadhyayG. OlefskyJ.M. SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity.Am. J. Physiol. Endocrinol. Metab.20102983E419E42810.1152/ajpendo.00417.200919996381
     [Google Scholar]
  89. SinghC.K. ChhabraG. NdiayeM.A. Garcia-PetersonL.M. MackN.J. AhmadN. The Role of Sirtuins in Antioxidant and Redox Signaling.Antioxid. Redox Signal.201828864366110.1089/ars.2017.729028891317
     [Google Scholar]
  90. YuW. Dittenhafer-ReedK.E. DenuJ.M. SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates mitochondrial redox status.J. Biol. Chem.201228717140781408610.1074/jbc.M112.35520622416140
     [Google Scholar]
  91. LiuS.S. WuF. JinY.M. ChangW.Q. XuT.M. HDAC11: A rising star in epigenetics.Biomed. Pharmacother.202013111060710.1016/j.biopha.2020.11060732841898
     [Google Scholar]
  92. Barcena-VarelaM. ColynL. Fernandez-BarrenaM.G. Epigenetic Mechanisms in Hepatic Stellate Cell Activation During Liver Fibrosis and Carcinogenesis.Int. J. Mol. Sci.20192010250710.3390/ijms2010250731117267
     [Google Scholar]
  93. PerugorriaM.J. WilsonC.L. ZeybelM. WalshM. AminS. RobinsonS. WhiteS.A. BurtA.D. OakleyF. TsukamotoH. MannD.A. MannJ. Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation.Hepatology20125631129113910.1002/hep.2575422488473
     [Google Scholar]
  94. LianZ. XuY. WangX. GongJ. LiuZ. Suppression of histone deacetylase 11 promotes expression of IL-10 in Kupffer cells and induces tolerance following orthotopic liver transplantation in rats.J. Surg. Res.2012174235936810.1016/j.jss.2010.12.03521392795
     [Google Scholar]
  95. ZhuangS. Regulation of STAT signaling by acetylation.Cell. Signal.20132591924193110.1016/j.cellsig.2013.05.00723707527
     [Google Scholar]
  96. HuangJ. WangL. DahiyaS. BeierU.H. HanR. SamantaA. BergmanJ. SotomayorE.M. SetoE. KozikowskiA.P. HancockW.W. Histone/protein deacetylase 11 targeting promotes Foxp3+ Treg function.Sci. Rep.201771862610.1038/s41598‑017‑09211‑328819166
     [Google Scholar]
  97. SunL. Marin de EvsikovaC. BianK. AchilleA. TellesE. PeiH. SetoE. Programming and Regulation of Metabolic Homeostasis by HDAC11.EBioMedicine20183315716810.1016/j.ebiom.2018.06.02529958910
     [Google Scholar]
  98. YangH. ChenL. SunQ. YaoF. MuhammadS. SunC. The role of HDAC11 in obesity‐related metabolic disorders: A critical review.J. Cell. Physiol.202123685582559110.1002/jcp.3028633481312
     [Google Scholar]
  99. BalaS. CsakT. KodysK. CatalanoD. AmbadeA. FuriI. LoweP. ChoY. Iracheta-VellveA. SzaboG. Alcohol-induced miR-155 and HDAC11 inhibit negative regulators of the TLR4 pathway and lead to increased LPS responsiveness of Kupffer cells in alcoholic liver disease.J. Leukoc. Biol.2017102248749810.1189/jlb.3A0716‑310R28584078
     [Google Scholar]
  100. GongD. ZengZ. YiF. WuJ. Inhibition of histone deacetylase 11 promotes human liver cancer cell apoptosis.Am. J. Transl. Res.201911298399030899397
     [Google Scholar]
  101. FreeseK. SeitzT. DietrichP. LeeS.M.L. ThaslerW.E. BosserhoffA. HellerbrandC. Histone deacetylase expressions in hepatocellular carcinoma and functional effects of histone deacetylase inhibitors on liver cancer cells in vitro.Cancers20191110158710.3390/cancers1110158731635225
     [Google Scholar]
  102. ChunP. Histone deacetylase inhibitors in hematological malignancies and solid tumors.Arch. Pharm. Res.201538693394910.1007/s12272‑015‑0571‑125653088
     [Google Scholar]
  103. YamaguchiT. CubizollesF. ZhangY. ReichertN. KohlerH. SeiserC. MatthiasP. Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progression.Genes Dev.201024545546910.1101/gad.55231020194438
     [Google Scholar]
  104. ZhangJ. ZhongQ. Histone deacetylase inhibitors and cell death.Cell. Mol. Life Sci.201471203885390110.1007/s00018‑014‑1656‑624898083
     [Google Scholar]
  105. LiZ. ZhuW.G. Targeting histone deacetylases for cancer therapy: From molecular mechanisms to clinical implications.Int. J. Biol. Sci.201410775777010.7150/ijbs.906725013383
     [Google Scholar]
  106. RhodesL.V. TateC.R. SegarH.C. BurksH.E. PhamduyT.B. HoangV. ElliottS. GilliamD. PounderF.N. AnbalaganM. ChriseyD.B. RowanB.G. BurowM.E. Collins-BurowB.M. Suppression of triple-negative breast cancer metastasis by pan-DAC inhibitor panobinostat via inhibition of ZEB family of EMT master regulators.Breast Cancer Res. Treat.2014145359360410.1007/s10549‑014‑2979‑624810497
     [Google Scholar]
  107. YooY.G. KongG. LeeM.O. Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1α protein by recruiting histone deacetylase 1.EMBO J.20062561231124110.1038/sj.emboj.760102516511565
     [Google Scholar]
  108. ZupkovitzG. GrausenburgerR. BrunmeirR. SeneseS. TischlerJ. JurkinJ. RemboldM. MeunierD. EggerG. LaggerS. ChioccaS. PropstF. WeitzerG. SeiserC. The cyclin-dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation.Mol. Cell. Biol.20103051171118110.1128/MCB.01500‑0920028735
     [Google Scholar]
  109. BhaskaraS. KnutsonS.K. JiangG. ChandrasekharanM.B. WilsonA.J. ZhengS. YenamandraA. LockeK. YuanJ. Bonine-SummersA.R. WellsC.E. KaiserJ.F. WashingtonM.K. ZhaoZ. WagnerF.F. SunZ.W. XiaF. HolsonE.B. KhabeleD. HiebertS.W. Hdac3 is essential for the maintenance of chromatin structure and genome stability.Cancer Cell201018543644710.1016/j.ccr.2010.10.02221075309
     [Google Scholar]
  110. GorospeM. de CaboR. AsSIRTing the DNA damage response.Trends Cell Biol.2008182778310.1016/j.tcb.2007.11.00718215521
     [Google Scholar]
  111. KotianS. LiyanarachchiS. ZelentA. ParvinJ.D. Histone deacetylases 9 and 10 are required for homologous recombination.J. Biol. Chem.2011286107722772610.1074/jbc.C110.19423321247901
     [Google Scholar]
  112. SimicP. WilliamsE.O. BellE.L. GongJ.J. BonkowskiM. GuarenteL. SIRT1 suppresses the epithelial-to-mesenchymal transition in cancer metastasis and organ fibrosis.Cell Rep.2013341175118610.1016/j.celrep.2013.03.01923583181
     [Google Scholar]
  113. GengH. HarveyC.T. PittsenbargerJ. LiuQ. BeerT.M. XueC. QianD.Z. HDAC4 protein regulates HIF1α protein lysine acetylation and cancer cell response to hypoxia.J. Biol. Chem.201128644380953810210.1074/jbc.M111.25705521917920
     [Google Scholar]
  114. TurtoiA. MottetD. MatheusN. DumontB. PeixotoP. HennequièreV. DeroanneC. ColigeA. De PauwE. BellahcèneA. CastronovoV. The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells.Angiogenesis201215454355410.1007/s10456‑012‑9279‑822584896
     [Google Scholar]
  115. KaluzaD. KrollJ. GesierichS. ManavskiY. BoeckelJ.N. DoebeleC. ZelentA. RössigL. ZeiherA.M. AugustinH.G. UrbichC. DimmelerS. Histone deacetylase 9 promotes angiogenesis by targeting the antiangiogenic microRNA-17-92 cluster in endothelial cells.Arterioscler. Thromb. Vasc. Biol.201333353354310.1161/ATVBAHA.112.30041523288173
     [Google Scholar]
  116. YangF.C. TanB.C.M. ChenW.H. LinY.H. HuangJ.Y. ChangH.Y. SunH.Y. HsuP.H. LiouG.G. ShenJ. ChangC.J. HanC.C. TsaiM.D. LeeS.C. Reversible acetylation regulates salt-inducible kinase (SIK2) and its function in autophagy.J. Biol. Chem.201328896227623710.1074/jbc.M112.43123923322770
     [Google Scholar]
  117. OehmeI. LinkeJ.P. BöckB.C. MildeT. LodriniM. HartensteinB. WiegandI. EckertC. RothW. KoolM. KadenS. GröneH.J. SchulteJ.H. LindnerS. Hamacher-BradyA. BradyN.R. DeubzerH.E. WittO. Histone deacetylase 10 promotes autophagy-mediated cell survival.Proc. Natl. Acad. Sci. USA201311028E2592E260110.1073/pnas.130011311023801752
     [Google Scholar]
  118. ScottA.M. WolchokJ.D. OldL.J. Antibody therapy of cancer.Nat. Rev. Cancer201212427828710.1038/nrc323622437872
     [Google Scholar]
  119. ShiF. LiY. HanR. FuA. WangR. NusbaumO. QinQ. ChenX. HouL. ZhuY. Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications.Sci. Rep.2021111251910.1038/s41598‑021‑81620‑x33510252
     [Google Scholar]
  120. LeeY.S. LimK.H. GuoX. KawaguchiY. GaoY. BarrientosT. OrdentlichP. WangX.F. CounterC.M. YaoT.P. The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis.Cancer Res.200868187561756910.1158/0008‑5472.CAN‑08‑018818794144
     [Google Scholar]
  121. BoyaultC. SadoulK. PabionM. KhochbinS. HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination.Oncogene200726375468547610.1038/sj.onc.121061417694087
     [Google Scholar]
  122. GuW. RoederR.G. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain.Cell199790459560610.1016/S0092‑8674(00)80521‑89288740
     [Google Scholar]
  123. HanR. NusbaumO. ChenX. ZhuY. Valeric acid suppresses liver cancer development by acting as a novel HDAC inhibitor.Mol. Ther. Oncolytics20201981810.1016/j.omto.2020.08.01733024815
     [Google Scholar]
  124. WynnT.A. Cellular and molecular mechanisms of fibrosis.J. Pathol.2008214219921010.1002/path.227718161745
     [Google Scholar]
  125. Van BenedenK. MannaertsI. PauwelsM. Van den BrandenC. van GrunsvenL.A. HDAC inhibitors in experimental liver and kidney fibrosis.Fibrogenesis Tissue Repair201361110.1186/1755‑1536‑6‑123281659
     [Google Scholar]
  126. MannaertsI. NuyttenN.R. RogiersV. VanderkerkenK. van GrunsvenL.A. GeertsA. Chronic administration of valproic acid inhibits activation of mouse hepatic stellate cells in vitro and in vivo.Hepatology201051260361410.1002/hep.2333419957378
     [Google Scholar]
  127. CetinkayaM. CansevM. CekmezF. TaymanC. CanpolatF.E. KafaI.M. YaylagulE.O. KramerB.W. SariciS.U. Protective effects of valproic acid, a histone deacetylase inhibitor, against hyperoxic lung injury in a neonatal rat model.PLoS One2015105e012602810.1371/journal.pone.012602825938838
     [Google Scholar]
  128. AherJ.S. KhanS. JainS. TikooK. JenaG. Valproate ameliorates thioacetamide-induced fibrosis by hepatic stellate cell inactivation.Hum. Exp. Toxicol.2015341445510.1177/096032711453199224812151
     [Google Scholar]
  129. ZhouN. MoradeiO. RaeppelS. LeitS. FrechetteS. GaudetteF. PaquinI. BernsteinN. BouchainG. VaisburgA. JinZ. GillespieJ. WangJ. FournelM. YanP.T. Trachy-BourgetM.C. KalitaA. LuA. RahilJ. MacLeodA.R. LiZ. BestermanJ.M. DelormeD. Discovery of N -(2-Aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide (MGCD0103), an orally active histone deacetylase inhibitor.J. Med. Chem.200851144072407510.1021/jm800251w18570366
     [Google Scholar]
  130. LiaoB. SunQ. YuanY. YinY. QiaoJ. JiangP. Histone deacetylase inhibitor MGCD0103 causes cell cycle arrest, apoptosis, and autophagy in liver cancer cells.J. Cancer20201171915192610.7150/jca.3409132194803
     [Google Scholar]
  131. MottamalM. ZhengS. HuangT. WangG. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents.Molecules20152033898394110.3390/molecules2003389825738536
     [Google Scholar]
  132. HuangR.X. ZhouP.K. DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer.Signal Transduct. Target. Ther.2020516010.1038/s41392‑020‑0150‑x32355263
     [Google Scholar]
  133. DewidarB. MeyerC. DooleyS. Meindl-BeinkerN. TGF-β in hepatic stellate cell activation and liver fibrogenesis—updated 2019.Cells2019811141910.3390/cells811141931718044
     [Google Scholar]
  134. WangY. ZhaoL. JiaoF.Z. ZhangW.B. ChenQ. GongZ.J. Histone deacetylase inhibitor suberoylanilide hydroxamic acid alleviates liver fibrosis by suppressing the transforming growth factor-β1 signal pathway.Hepatobiliary Pancreat. Dis. Int.201817542342910.1016/j.hbpd.2018.09.01330249543
     [Google Scholar]
  135. ÖzelM. BaskolM. AkalınH. BaskolG. Suberoylanilide hydroxamic acid (SAHA) reduces fibrosis markers and deactivates human stellate cells via the epithelial–mesenchymal transition (EMT).Cell Biochem. Biophys.202179234935710.1007/s12013‑021‑00974‑133689126
     [Google Scholar]
  136. SanaeiM. KavoosiF. Histone deacetylase inhibitors, intrinsic and extrinsic apoptotic pathways, and epigenetic alterations of histone deacetylases (HDACs) in hepatocellular carcinoma.Iran. J. Pharm. Res.202120332433610.22037/ijpr.2021.115105.1519734903992
     [Google Scholar]
  137. MaJ. WangY. DingJ. ZhangS. YangY. SunC. SAHA induces white fat browning and rectifies metabolic dysfunctions via activation of ZFPs.J. Endocrinol.2021249317719310.1530/JOE‑20‑047233856361
     [Google Scholar]
  138. KaimoriA. PotterJ.J. ChotiM. DingZ. MezeyE. KoteishA.A. Histone deacetylase inhibition suppresses the transforming growth factor beta1-induced epithelial-to-mesenchymal transition in hepatocytes.Hepatology20105231033104510.1002/hep.2376520564330
     [Google Scholar]
  139. GrayS.G. YakovlevaT. HartmannW. TallyM. BakalkinG. EkströmT.J. IGF-II enhances trichostatin A-induced TGFbeta1 and p21(Waf1,Cip1, sdi1) expression in Hep3B cells.Exp. Cell Res.1999253261862810.1006/excr.1999.466110585285
     [Google Scholar]
  140. FinninM.S. DonigianJ.R. CohenA. RichonV.M. RifkindR.A. MarksP.A. BreslowR. PavletichN.P. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors.Nature1999401674918819310.1038/4371010490031
     [Google Scholar]
  141. ZhangQ. YangF. LiX. WangL. ChuX. ZhangH. GongZ. Trichostatin A protects against experimental acute-on-chronic liver failure in rats through regulating the acetylation of nuclear factor-κB.Inflammation20153831364137310.1007/s10753‑014‑0108‑725604312
     [Google Scholar]
  142. DingD. ChenL.L. ZhaiY.Z. HouC.J. TaoL.L. LuS.H. WuJ. LiuX.P. Trichostatin A inhibits the activation of Hepatic stellate cells by increasing C/EBP-α acetylation in vivo and in vitro.Sci. Rep.201881439510.1038/s41598‑018‑22662‑629535398
     [Google Scholar]
  143. ShenM. SunL. LiuX. XiongM. LiS. TangA. ZhangG. Trichostatin A improves the inflammatory response and liver injury in septic mice through the FoxO3a/autophagy signaling pathway.World J. Emerg. Med.202213318218810.5847/wjem.j.1920‑8642.2022.05635646203
     [Google Scholar]
  144. HeroldC. GanslmayerM. OckerM. HermannM. GeertsA. HahnE.G. SchuppanD. The histone-deacetylase inhibitor Trichostatin A blocks proliferation and triggers apoptotic programs in hepatoma cells.J. Hepatol.200236223324010.1016/S0168‑8278(01)00257‑411830335
     [Google Scholar]
  145. RamalingamS.S. KummarS. SarantopoulosJ. ShibataS. LoRussoP. YerkM. HolleranJ. LinY. BeumerJ.H. HarveyR.D. IvyS.P. BelaniC.P. EgorinM.J. Phase I study of vorinostat in patients with advanced solid tumors and hepatic dysfunction: A national cancer institute organ dysfunction working group study.J. Clin. Oncol.201028294507451210.1200/JCO.2010.30.230720837947
     [Google Scholar]
  146. GordonS.W. McGuireW.P.III ShaferD.A. SterlingR.K. LeeH.M. MatherlyS.C. RobertsJ.D. BoseP. TombesM.B. ShraderE.E. RyanA.A. KmieciakM. NguyenT. DengX. BandyopadhyayD. DentP. PoklepovicA.S. PhaseI. Phase I study of sorafenib and vorinostat in advanced hepatocellular carcinoma.Am. J. Clin. Oncol.201942864965410.1097/COC.000000000000056731305287
     [Google Scholar]
  147. El-KhoueiryA.B. O’DonnellR. SemradT.J. MackP. BlanchardS. BaharyN. JiangY. YenY. WrightJ. ChenH. LenzH.J. GandaraD.R. A phase I trial of escalating doses of cixutumumab (IMC-A12) and sorafenib in the treatment of advanced hepatocellular carcinoma.Cancer Chemother. Pharmacol.201881595796310.1007/s00280‑018‑3553‑429520435
     [Google Scholar]
  148. YoonS. KangG. EomG.H. HDAC inhibitors: Therapeutic potential in fibrosis-associated human diseases.Int. J. Mol. Sci.2019206132910.3390/ijms2006132930884785
     [Google Scholar]
/content/journals/ijghd/10.2174/0126662906313034241223071431
Loading
Histone Deacetylase Inhibitors Promising Therapeutic Target for Liver Diseases
Int J Gastroenterol Hepatol Dis 4, E26662906313034 (2025); https://doi.org/10.2174/0126662906313034241223071431
/content/journals/ijghd/10.2174/0126662906313034241223071431
/content/journals/ijghd/10.2174/0126662906313034241223071431
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): HDAC inhibitors; hepatitis C virus; hepatocellular carcinoma; hepatoprotective agents; Histone deacetylases; liver diseases

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test