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Review

Histone Deacetylase Inhibitors In The Treatment Of Cancer: Overview And Perspectives

, , &
Pages 1439-1460 | Published online: 02 Aug 2012

References

  • Allfrey VG , FaulknerR, MirskyAE. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis.Proc. Natl Acad. Sci. USA51, 786–794 (1964).
  • Kleff S , AndrulisED, AndersonCW, SternglanzR. Identification of a gene encoding a yeast historic H4 acetyltransferase.J. Biol. Chem.270, 24674–24677 (1995).
  • Brownell JE , ZhouJ, RanalliTet al. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84, 843–851 (1996).
  • Taunton J , HassigCA, SchreiberSL. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p.Science272, 408–411 (1996).
  • Tanner KG , LandryJ, SternglanzR, DenuJM. Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose.Proc. Natl Acad. Sci. USA97, 14178–14182 (2000).
  • Martin M , KettmannR, DequiedtF. Class IIa histone deacetylases: regulating the regulators.Oncogene26, 5450–5467 (2007).
  • Grant S , EasleyC, KirkpatrickP. Vorinostat.Nat. Rev. Drug Discov.6, 21–22 (2007).
  • Breslow M . Dimethyl sulfoxide to vorinostat development of this histone deacetylase inhibitor as an anticancer drug.Nat. Biotechnol.25, 84–90 (2007).
  • VanderMolen KM , McCullochW, PearceCJ, OberliesNH. Romidepsin: a natural product recently approved for cutaneous T-cell lymphoma.J. Antibiot.64, 525–531 (2011).
  • Boumber Y , Issa J-PJ. Epigenetics in cancer: what’s the future. Oncology25, 1–13 (2011).
  • Biel M , WascholowskiV, GiannisA. Epigenetic – an epicenter of gene regulation: histones and histone-modifying enzymes.Angew. Chem. Int. Ed. Engl.44, 3186–3216 (2005).
  • Mai A , MassaS, RotiliDet al. Histone deacetylation in epigenetics: an attractive target for anticancer therapy. Med. Res. Rev. 3, 261–309 (2005).
  • Rodriquez M , AquinoM, BrunoI, De Martino G, Taddei M, Gomez-Paloma L. Chemistry and biology of chromatin remodeling agents: state of art and future perspective of HDAC inhibitors. Curr. Med. Chem.13, 1119–1139 (2006).
  • Petrella A , FontanellaB, CarratùA, BizzarroV, RodriquezM, ParenteL. Histone deacetylase inhibitors in the treatment of hematological malignancies.Mini Rev. Med. Chem.11, 519–527 (2011).
  • Kristeleit R , StimsonL, WorkmanP, AherneW. Histone modification enzymes: novel targets for cancer drugs.Expert Opin. Emerg. Drugs.9, 135–154 (2004).
  • Marks PA , RichonVM, MillerTA, KellyWK. Histone deacetylase inhibitors: new targeted anticancer drugs. In: Cancer: Principles and Practice of Oncology (7th Edition). DeVita VT Jr, Hellman S, Rosenberg SA (Eds). Lippincott Williams & Wilkins, Philadelphia, PA, USA, 439–445 (2005).
  • Peserico A , SimoneC. Physical and functional HAT/HDAC interplay regulates protein acetylation balance.J. Biomed. Biotechnol.371832 (2011).
  • Yang XJ , SetoE. The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men.Nat. Rev. Mol. Cell Biol.9, 206–218 (2008).
  • de Ruijter AJ , van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem. J.370, 737–749 (2003).
  • Gregoretti IV , LeeYM, GoodsonHV. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis.J. Mol. Biol.338, 17–31 (2004).
  • Marks PA . The clinical development of histone deacetylase inhibitors as targeted anticancer drugs.Expert Opin. Investig. Drugs19, 1049–1066 (2010).
  • Yang XJ , GrégoireS. Class II histone deacetylases: from sequence to function, regulation and clinical implication.Mol. Cell. Biol.25, 2873–2884 (2005).
  • Glozak MA , SenguptaN, ZhangX, SetoE. Acetylation and deacetylation of non-histone proteins.Gene363, 15–23 (2005).
  • Kim SC , SprungR, ChenYet al. Substrates and functional diversity of lysine acetylation revealed by a proteomics survey. Mol. Cell 23, 607–618 (2006).
  • Witt O , DeubzerHE, MildeY, OehmeI. HDAC family: what are the cancer relevant targets?Cancer Lett.277, 8–21 (2009).
  • Lemoine M , YounesA. Histone deacetylase inhibitors in the treatment of lymphoma.Discov. Med.10, 462–470 (2010).
  • Dokmanovic M , ClarkeC, MarksPA. Histone deacetylase inhibitors: overview and perspectives.Mol. Cancer Res.5, 981–989 (2007).
  • Chang S , McKinseyTA, ZhangCL, RichardsonJA, HillJA, OlsonEN. Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development.Mol. Cell. Biol.24, 8467–8476 (2004).
  • McKinsey TA , OlsonEN. Cardiac histone acetylation – therapeutic opportunities abound.Trends Genet.20, 206–213 (2004).
  • McKinsey TA , OlsonEN. Toward transcriptional therapies for the failing heart: chemical screens to modulate genes.J. Clin. Invest.115, 538–546 (2005).
  • Ng HH , BirdA. Histone deacetylases: silencers for hire.Trends Biochem. Sci.25, 121–126 (2000).
  • Legube G , TroucheD. Regulating histone acetyltransferases and deacetylases.EMBO Reports Rev.4, 944–947 (2003).
  • Rayman JB , TakahashiY E2F mediates cell cycle-dependent transcriptional repression in vivo by recruitment of an HDAC1/mSin3B corepressor complex. Genes Dev.16, 933–947 (2002).
  • Balciunaite E , SpektorA. Pocket protein complexes are recruited to distinct targets in quiescent and proliferating cells.Mol. Cell. Biol.25, 8166–8178 (2005).
  • Knoepfler PS , EisenmanRN. Sin meets NuRD and other tails of repression.Cell99, 447–450 (1999).
  • Lunyak VV , BurgessR, PrefontaineGGet al. Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science 298, 1747–1752 (2002).
  • Fischle W , DequiedtF, HendzelMJet al. Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/NCoR. Mol. Cell 9, 45–57 (2002).
  • Chan JK , SunL, YangXJ, ZhuG, WuZ. Functional characterization of an amino-terminal region of HDAC4 that possesses MEF2 binding and transcriptional repressive activity.J. Biol. Chem.278, 23515–23521 (2003).
  • Fischle W , DequiedtF, FillionM, HendzelMJ, VoelterW, VerdinE. Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo. J. Biol. Chem.276, 35826–35835 (2001).
  • Lahm A , PaoliniC, PallaoroMet al. Unraveling the Hidden Catalytic Activity of Vertebrate Class IIa Histone Deacetylases. Proc. Natl Acad. Sci. USA 104, 17335–17340 (2007).
  • Hockly E , RichonVM, WoodmanBet al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc. Natl Acad. Sci. USA 100, 2041–2046 (2003).
  • Bottomley MJ , Lo SurdoP, Di GiovinePet al. Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain. J. Biol. Chem.283, 26694–26704 (2008).
  • Beumer JH , TawbiH. Role of histone deacetylases and their inhibitors in cancer biology and treatment.Curr. Clin. Pharmacol.5, 196–208 (2010).
  • Marquard L , GjerdrumLM, ChristensenIJ, JensenPB, SehestedM, RalfkiaerE. Prognostic significance of the therapeutic targets histone deacetylase 1, 2, 6 and acetylated histone H4 in cutaneous T-cell lymphoma.Histopathology53, 267–277 (2008).
  • Weichert W . HDAC expression and clinical prognosis in human malignancies.Cancer Lett.280, 168–176 (2009).
  • Taunton J , CollinsJL, SchreiberSL. Synthesis of natural and modified trapoxins, useful reagents for exploring histone deacetylase function.J. Am. Chem. Soc.118, 10412–10422 (1996).
  • Glaser KB , LiJ, PeaseLJet al. Differential protein acetylation induced by novel histone deacetylase inhibitors. Biochem. Biophys. Res. Commun. 325, 683–690 (2004).
  • Bertrand P . Inside HDAC with HDAC inhibitors.Eur. J. Med. Chem.45, 2095–2116 (2010).
  • Yadong C , HuifangL, WanquanTet al. 3D-QSAR studies of HDACs inhibitors using pharmacophore-based alignment. Eur. J.Med. Chem. 44, 2868–2876 (2009).
  • Noureen N , KalsoomS, RashidH. Ligand based pharmacophore modelling of anticancer histone deacetylase inhibitors.Afr. J. Biotech.9, 3923–3931 (2010).
  • Richon VM , WebbY, MergerRet al. Second generation hybrid polar compounds are potent inducers of transformed cell differentiation. Proc. Natl Acad. Sci. USA 93, 5705–5708 (1996).
  • Butler LM , AgusDB, ScherHIet al. Suberoylanilide hydroxamic acid, an in vivo inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. Cancer Res. 60, 5165–5170 (2000).
  • Reuben RC , WifeRL, BreslowR, RifkindRA, MarksPA. A new group of potent inducers of differentiation in murine erythroleukemia cells.Proc. Natl Acad. Sci. USA73, 862–866 (1976).
  • Su GH , SohnTA, RyuB, KernSE. A novel histone deacetylase inhibitor identified by high-throughput transcriptional screening of compound library.Cancer Res.60, 3137–3142 (2000).
  • Wong JC , HongR, SchreiberSL. Structural biasing elements for in-cell histone deacetylase paralog selectivity.J. Am. Chem. Soc.125, 5586–5587 (2003).
  • Hanessian S , VinciV, AuzzasL, MarziM, GianniniG. Exploring alternative Zn-binding groups in the design of HDAC inhibitors: squaric acid, N-hydroxylurea and oxazoline analogues of SAHA.Bioorg. Med. Chem. Lett.16, 4784–4787 (2006).
  • Hanessian S , AuzzasL, GianniniGet al. Omega-alkoxy analogues of SAHA (vorinostat) as inhibitors of HDAC: a study of chain-length and stereochemical dependence. Bioorg. Med. Chem. Lett. 17, 6261–6265 (2007).
  • Kozikowski AP , TapadarS, LuchiniDN, KimKH, BilladeauDD. Isoxazole moiety in the linker region of HDAC inhibitors adjacent to the Zn-chelating group: effects on the HDAC biology and antiproliferative activity.J. Med. Chem.51, 4370–4373 (2008).
  • Giannini G , MarziM, PezziRet al. N-Hydroxy-(4-oxime)-cinnamide: a versatile scaffold for the synthesis of novel histone deacetylase. Bioorg. Med. Chem. Lett. 19, 2346–2349 (2009).
  • Auzzas L , LarssonA, MateraRet al. Non-natural macrocyclic inhibitors of histone deacetylase: design, synthesis and activity. J. Med. Chem., 53, 8387–8399 (2010).
  • Zhang Y , FangH, FengJ, JiaY, WangX, XuW. Discovery of a tetrahydroisoquinoline-based hydroxamic acid derivative (ZYJ-34c) as histone deacetylase inhibitor with potent oral antitumor activities.J. Med. Chem.54, 5532–5539 (2011).
  • Tsuji N , KobayashiM, NagashimaK, WakisakaY, KoizumiK. A new antifungal antibiotic, trichostatin.J. Antibiot.29, 1–6 (1976).
  • Mori K , KosekiK. Synthesis of trichostatin A, a potent differentiation inducer of Friend-leukemic cells and its antipode.Tetrahedron44, 6013–6020 (1988).
  • Remiszewski SW , SambucettiLC, BairKWet al. N-hydroxy-3-phenyl-2-propenamides as novel inhibitors of human histone deacetylase with in vivo antitumor activity: discovery of NVP-LAQ824. J. Med. Chem. 46, 4609–4624 (2003).
  • Li KW , WuJ, XingW, SimonJA. Total synthesis of the antitumor depsipeptide FR-901, 228.J. Am. Chem. Soc.118, 7237–7238 (1996).
  • Furumai R , MatsuyamaA, KobashiNet al. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res. 62, 4916–4921 (2002).
  • Ueda H , NakajiamH, HoriYet al. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromabacterium violaceum. J. Antibiot. 47, 301–310. (1994).
  • Closse A , HugueninR. Isolierung und Strukturaufklärung von Chlamydocin.Helv. Chim. Acta57, 533–545 (1974).
  • Gross ML , McCreryD, CrowFet al. The structure of the toxin from helminthosporium carbonum. Tetrahedron Lett. 23, 5381–5384 (1982).
  • Umehara K , NakaharaK, KijotoSet al. Studies on WF-3161, a new antitumor antibiotic. J. Antibiot. 36, 478–483 (1983).
  • Schmidt U , BeutlerU, LieberknechtA. Total synthesis of the antitumor antibiotic WF-3161.Angew. Int. Ed.28, 333–334 (1989).
  • Itazaki H , NagashimaK, SugitaKet al. Isolation and structural elucidation of new cyclotetrapeptides, trapoxins A and B, having detransformation activities as antitumor agents. J. Antibiot. 43, 1524–1532 (1990).
  • Kijima M , YoshidaM, SugitaK, HorinouchiS, BeppuT. Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase.J. Biol. Chem.268, 22429–22435 (1993).
  • Darkin-Rattray SJ , GurnettAM, MyersRWet al. Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase. Proc. Natl Acad. Sci. USA 93, 13143–13147 (1996).
  • Singh SB , ZinkDL, LieschJMet al. Structure and chemistry of apicidins, a class of novel cyclic tetrapeptides without a terminal α-keto epoxide as inhibitors of histone deacetylase with potent antiprotozoal activities. J. Org. Chem. 67, 815–825 (2002).
  • Colletti SL , MyersRW, Darkin-RattraySJet al. Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 1. Bioorg. Med. Chem. Lett. 11, 107–111 (2001).
  • Colletti SL , MyersR W, Darkin-Rattray SJ et al. Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 2. Bioorg. Med. Chem. Lett.11, 113–117 (2001).
  • Mori H , UranoY, AbeFet al. FR235222, a fungal metabolite, is a novel immunosuppressant that inhibits mammalian histone deacetylase (HDAC). I. Taxonomy, fermentation, isolation and biological activities. J. Antibiot. 56, 72–79 (2003).
  • Xie W , ZouB, PeiD, MaD. Total synthesis of cyclic tetrapeptide FR235222, a potent immunosuppressant that inhibits mammalian histone deacetylases.Org. Lett.7, 2775–2777 (2005).
  • Rodriquez M , TerraccianoS, CiniEet al. Total synthesis, NMR solution structure, and binding model of the potent histone deacetylase inhibitor FR235222. Angew. Chem. Int. Ed. Engl. 45, 423–427 (2006).
  • Gomez-Paloma L , BrunoI, CiniEet al. Design and synthesis of cyclopeptide analogues of the potent histone deacetylase inhibitor FR235222. ChemMedChem 2, 1511–1519 (2007).
  • Di Micco S , TerraccianoS, BrunoIet al. Molecular modeling studies toward the structural optimization of new cyclopeptide-based HDAC inhibitors modeled on the natural product FR235222. Bioorg. Med. Chem. 16, 8635–8642 (2008).
  • Suzuki T . Synthesis and histone deacetylase inhibitory activity of new benzamide derivatives.J. Med. Chem.42, 3001–3003 (1999).
  • El-Beltagi HM , MartensACM, LelievedP, HarounEA, HagenbeekA. Acetyldinaline: a new oral cytostatic drug with impressive differential activity against leukemic cells and normal stem cell.Cancer Res.53, 3008–3014 (1993).
  • Vaisburg A , BernsteinN, FrechetteSet al. (2-amino-phenyl)-amides of omega-substituted alkanoic acids as new histone deacetylase inhibitors. Bioorg. Med. Chem Lett. 14, 283–287 (2004).
  • Frey RR , WadaCK, GarlandRBet al. Trifluoromethylketones as inhibitors of histone deacetylase. Bioorg. Med. Chem. Lett. 12, 3443–3447 (2002).
  • Vasudevan A , JiZ, FreyRRet al. Heterocyclic ketones as inhibitors of histone deacetylase. Biooorg. Med. Chem. Lett. 13, 3909–3913 (2003).
  • Galletti P , QuintavallaA, VentriciCet al. Azetidinones as zinc-binding groups to design selective HDAC8 inhibitors. ChemMedChem 4, 1991–2001 (2009).
  • Botta CB , CabriW, CiniEet al. Oxime amide as a novel zinc binding group in histone deacetylase inhibitors: synthesis, biological activity and computational evaluation. J. Med. Chem. 54, 2165–2182 (2011).
  • Ungerstedt JS , SowaY, XuWSet al. Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Proc. Natl Acad. Sci. USA 102, 673–678 (2005).
  • Bolden JE , PeartMJ, RickyW, JohnstoneRW. Anticancer activities of histone deacetylase inhibitors.Nat. Rev. Drug Discov.5, 769–784 (2006).
  • Van Lint C , EmilianiS, VerdinE. The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation.Gene Expr.5, 245–253 (1996).
  • Glaser KB , StaverMJ, WaringJF, StenderJ, UlrichRG, DavidsenSK. Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines.Mol. Cancer Ther.2, 151–163 (2003).
  • Richon VM , SandhoffTW, RifkindRA, MarksPA. Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation.Proc. Natl Acad. Sci. USA97, 10014–10019 (2000).
  • Xu Y . Regulation of p53 responses by posttranslational modifications.Cell Death Diff.10, 400–403 (2003).
  • Jin YH , JeonEJ, LiQLet al. Transforming growth factor -beta stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated degradation. J. Biol. Chem. 279, 29409–29417 (2004).
  • Chi XZ , YangJO, LeeKYet al. RUNX3 suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1) expression in cooperation with transforming growth factor {beta}-activated SMAD. Mol. Cell. Biol. 25, 8097–8107. (2005).
  • Yano T , ItoK, FukamachiHet al. The RUNX3 tumor suppressor upregulates Bim in gastric epithelial cells undergoing transforming growth factor betainduced apoptosis. Mol. Cell. Biol. 26, 4474–4488 (2006).
  • Rascle A , JohnstonJA, AmatiB. Deacetylase activity is required for recruitment of the basal transcription machinery and transactivation by STAT5.Mol. Cell. Biol.23, 4162–4173 (2003).
  • Wang LG , OssowskiL, FerrariAC. Androgen receptor level controlled by a suppressor complex lost in an androgen-independent prostate cancer cell line.Oncogene23, 5175–5184 (2004).
  • Lee EM , ShinS, ChaHJet al. Suberoylanilide hydroxamic acid (SAHA) changes microRNA expression profiles in A549 human non-small cell lung cancer cells. Int. J. Mol. Med. 24, 45–50 (2009).
  • Burgess A , RuefliA, BeamishHet al. Histone deacetylase inhibitors specifically kill nonproliferating tumour cells. Oncogene 23, 6693–6701 (2004).
  • Zhang Y , AdachiM, KawamuraR, ImaiK. Bmf is a possible mediator in histone deacetylase inhibitors FK228 and CBHA-induced apoptosis.Cell Death Differ.13, 129–140. (2006).
  • Zhao Y , TanJ, ZhuangL, JiangX, LiuET, YuQ. Inhibitors of histone deacetylases target the Rb-E2F1 pathway for apoptosis induction through activation of proapoptotic protein Bim.Proc. Natl Acad. Sci. USA102, 16090–16095 (2005).
  • Johnstone RW . Histone-deacetylase inhibitors: novel drugs for the treatment of cancer.Nat. Rev. Drug Discov.1, 287–299 (2002).
  • Insinga A , MonestiroliS, RonzoniSet al. Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway. Nat. Med. 11, 71–76 (2005).
  • Borbone E , BerlingieriMT, De Bellis F et al. Histone deacetylase inhibitors induce thyroid cancer-specific apoptosis through proteasome-dependent inhibition of TRAIL degradation. Oncogene29, 105–116 (2010).
  • D‘Acunto CW , CarratuA, RodriquezM, TaddeiM, ParenteL, PetrellaA. LGP1, a histone deacetylase inhibitor analogue of FR235222, sensitizes promyelocytic leukaemia U937 cells to TRAIL-mediated apoptosis.Anticancer Res.30, 887–894 (2010).
  • Petrella A , FestaM, ErcolinoSFet al. Annexin-1 downregulation in thyroid cancer correlates to the degree of tumour differentiation. Cancer Biol. Ther. 5, 643–647 (2006).
  • Garcia Pedrero JM , FernandezMP, MorganROet al. Annexin A1 down-regulation in head and neck cancer is associated with epithelial differentiation status. Am. J. Pathol., 164, 73–79 (2004).
  • D‘Acunto CW , FontanellaB, RodriquezM, TaddeiM, ParenteL, PetrellaA. Histone deacetylase inhibitor FR235222 sensitizes human prostate adenocarcinoma cells to apoptosis through up-regulation of Annexin A1.Cancer Lett.295, 85–91 (2010).
  • Petrella A , D‘AcuntoCW, RodriquezMet al. Effects of FR23S222, a novel HDAC inhibitor, in proliferation and apoptosis of human leukaemia cell lines: role of annexin A1. Eur. J. Cancer 44, 740–749 (2008).
  • Xu W , NgoL, PerezG, DokmanovicM, MarksPA. Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor.Proc. Natl Acad. Sci. USA103, 15540–15545 (2006).
  • Xu WS , ParmigianiRB, MarksPA. Histone deacetylase inhibitors: molecular mechanisms of action.Oncogene26, 5541–5552 (2007).
  • Drummond DC , NobleCO, KirpotinDB, GuoZ, ScottGK, BenzCC. Clinical development of histone deacetylase inhibitors as anticancer agents.Annu. Rev. Pharmacol. Toxicol.45, 495–528 (2005).
  • Atadja PW . HDAC inhibitors and cancer therapy, epigenetics and disease.Prog. Drug Res.67, 175–195 (2011).
  • Cimini D , MattiuzzoM, TorosantucciL, DegrassiF. Histone hyperacetylation in mitosis prevents sister chromatid separation and produces chromosome segregation defects.Mol. Biol. Cell14, 3821–3833 (2003).
  • Taddei A , MaisonC, RocheD, AlmouzniG. Reversible disruption of pericentric heterochromatin and centromere function by inhibiting deacetylases.Nat. Cell. Biol.3, 114–120 (2001).
  • Dowling M , VoongKR, KimM, KeutmannMK, HarrisE, KaoGD. Mitotic spindle checkpoint inactivation by trichostatin a defines a mechanism for increasing cancer cell killing by microtubule-disrupting agents.Cancer Biol. Ther.4, 197–206 (2005).
  • Robbins AR , JablonskiSA, YenTJet al. Inhibitors of histone deacetylases alter kinetochore assembly by disrupting pericentromeric heterochromatin. Cell Cycle 4, 717–726 (2005).
  • Ruefli AA , AusserlechnerMJ, BernhardDet al. The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species. Proc. Natl Acad. Sci. USA 98, 10833–10838 (2001).
  • Rosato RR , AlmenaraJA, GrantS. The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1.Cancer Res.63, 3637–3645 (2003).
  • Ellis L , HammersH, PiliR. Targeting tumor angiogenesis with histone deacetylase inhibitors.Cancer Lett.280, 145–153 (2009).
  • Jeong JW , BaeMK, AhnMYet al. Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. Cell 111, 709–720 (2002).
  • Deroanne CF , BonjeanK, ServotteSet al. Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene 21, 427–436 (2002).
  • Carew JS , GilesFJ, NawrockiST. Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy.Cancer Lett.269, 7–17 (2008).
  • Liang D , KongX, SangN. Effects of histone deacetylase inhibitors on HIF-1.Cell Cycle5, 2430–2435 (2006).
  • Kong X , LinZ, LiangD, FathD, SangN, CaroJ. Histone deacetylase inhibitors induce VHL and ubiquitin-independent proteasomal degradation of hypoxia-inducible factor1 alpha.Mol. Cell. Biol.26, 2019–2028 (2006).
  • Qian DZ , KachhapSK, CollisSJet al. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res. 66, 8814–8821 (2006).
  • Naldini A , FilippiI, CiniE, RodriquezM, CarraroF, TaddeiM. Downregulation of Hypoxia-related Responses by Novel Antitumor Histone Deacetylase Inhibitors in MDAMB231 Breast Cancer Cells.Anticancer Agents Med. Chem.12(4), 407–413 (2011).
  • Kim SO , ChoiBT, Choi I-W et al. Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells. BMB Reports42, 655–660 (2009).
  • Qureshi IA , MehlerMF. Epigenetics, nervous system tumors, and cancer stem cells.Cancers3, 3525–3556 (2011).
  • Farrell A . A close look at cancer.Nat. Med.17, 262–265 (2011).
  • Marks PA , XuWS. Histone deacetylase inhibitors: potential in cancer therapy.J. Cell. Biochem.107, 600–608 (2009).
  • Haberland M , MontgomeryRL, OlsonEN. The many roles of histone deacetylases in development and physiology: implications for disease and therapy.Nat. Rev. Genet.10, 32–42 (2009).
  • Wagner JM , HackansonB, LübbertM, JungM. Therapy in combination.Clin. Epigenet.1, 117–136 (2010).
  • Wang H , DymockBW. New patented histone deacetylase inhibitors.Expert Opin. Ther. Pat.19, 1727–1757 (2009).
  • Suzuki T . Explorative study on isoform-selective histone deacetylase inhibitors.Chem. Pharm. Bull.57, 897–906 (2009).
  • Ma X , EzzeldinHH, DiasioRB. Histone deacetylase inhibitors: current status and overview of recent clinical trials.Drugs69, 1911–1934 (2009).
  • Bantscheff M , HopfC, SavitskiMet al. Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat. Biotechnol. 29, 255–265 (2011).
  • La Thangue NB , KerrDJ. Predictive biomarkers: a paradigm shift towards personalized cancer medicine.Nat. Rev. Clin. Oncol.8, 587–596 (2011).
  • Fotheringham S , EppingMT, StimsonLet al. Genome-wide loss-of-function screen reveals an important role for the proteasome in HDAC inhibitor-induced apoptosis. Cancer Cell 15, 57–66 (2009).
  • Khan O , FotheringhamS, WoodVet al. HR23B is a biomarker for tumor sensitivity to HDAC inhibitor-based therapy. Proc. Natl Acad. Sci. USA 107, 6532–6537 (2010).
  • Jennifer LB ,Yongyao X, Susanne JS et al. Histone deacetylase activities are required for innate immune cell control of Th1 but not Th2 effector cell function. Blood109, 1123–1130 (2007).
  • Adcock IM . HDAC inhibitors as anti-inflammatory agents.Br. J. Pharmacol.150, 829–831 (2007).
  • Routy JP . Valproic acid: a potential role in treating latent HIV infection.Lancet366, 523–524 (2005).
  • Andrews KT , HaqueA, JonesMK. HDAC inhibitors in parasitic diseases.Immunol. Cell Biol.90, 66–77 (2012).
  • Fischer A , SananbenesiF, WangX, DobbinM, Tsai L-H. Recovery of learning and memory is associated with chromatin remodelling. Nature447, 178–182 (2007).
  • Chuang D -M, Leng Y, Marinova Z, Kim H-J, Chiu C-T. Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci.32, 591–601 (2009).
  • Butler R , BatesGP. Histone deacetylase inhibitors as therapeutics for polyglutamine disorders.Nat. Rev. Neurosci.7, 784–796 (2006).
  • Cao H , JungM, StamatoyannopoulosG. Hydroxamide derivatives of short chain fatty acid have erythropoietic activity and induce γ-gene expression in vivo. Exp. Hematol.33, 1443–1449 (2005).
  • Minetti GC , ColussiC, AdamiRet al. Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors. Nat. Med. 12, 1147–1150 (2006).
  • Lin HS , HuCY, ChanHYet al. Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. Br. J. Pharmacol. 150, 862–872 (2007).
  • Romagnani P , LasagniL, MazzinghiB, LazzeriE, RomagnaniS. Pharmacological modulation of stem cell function.Curr. Med. Chem.14, 1129–1139 (2007).
  • Khan O , La Thangue NB. HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications. Immunol. Cell Biol.90, 85–94 (2012).

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