Histone-deacetylase inhibitors: novel drugs for the treatment of cancer

The opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs) allow gene expression to be exquisitely regulated through chromatin remodelling. Aberrant transcription due to altered expression or mutation of genes that encode HATs, HDACs or their binding partners, is a key event in the onset and progression of cancer. HDAC inhibitors can reactivate gene expression and inhibit the growth and survival of tumour cells. The remarkable tumour specificity of these compounds, and their potency in vitro and in vivo, underscore the potential of HDAC inhibitors as exciting new agents for the treatment of cancer.

[1]  T. Owen-Hughes,et al.  Mechanisms for ATP-dependent chromatin remodelling. , 2001, Biochemical Society transactions.

[2]  R. Yarden,et al.  BRCA1 interacts with components of the histone deacetylase complex. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Manfred Jung,et al.  Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates. , 2002, Journal of medicinal chemistry.

[4]  E. Verdin,et al.  BCoR, a novel corepressor involved in BCL-6 repression. , 2000, Genes & development.

[5]  S. Grossman,et al.  p300/CBP/p53 interaction and regulation of the p53 response. , 2001, European journal of biochemistry.

[6]  T. Ekström,et al.  The human histone deacetylase family. , 2001, Experimental cell research.

[7]  Up-regulation of costimulatory/adhesion molecules by histone deacetylase inhibitors in acute myeloid leukemia cells. , 2000 .

[8]  R. Bürli,et al.  Sequence-specific DNA recognition by polyamides. , 1999, Current opinion in chemical biology.

[9]  D. Green.  Apoptotic Pathways Paper Wraps Stone Blunts Scissors , 2000, Cell.

[10]  D. Reinberg,et al.  Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. , 2001, Genes & development.

[11]  F. Ece,et al.  Histone deacetylase inhibitor downregulation of bcl-xl gene expression leads to apoptotic cell death in mesothelioma. , 2001, American journal of respiratory cell and molecular biology.

[12]  P. Pandolfi,et al.  Histone deacetylase inhibitors induce remission in transgenic models of therapy-resistant acute promyelocytic leukemia. , 2001, The Journal of clinical investigation.

[13]  K. Blanchard,et al.  Acute mixed lineage leukemia with an inv(8)(p11q13) resulting in fusion of the genes for MOZ and TIF2. , 1998, Blood.

[14]  S. Baylin,et al.  DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci , 2000, Nature Genetics.

[15]  H. Saito,et al.  deacetylase inhibitors in acute myeloid leukemia cells Up-regulation of costimulatory / adhesion molecules by histone , 2000 .

[16]  D. Fairlie,et al.  Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells. , 2000, Molecular biology of the cell.

[17]  D. Bernhard,et 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 , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  G. Otterson,et al.  DNA methyltransferase inhibition enhances apoptosis induced by histone deacetylase inhibitors. , 2001, Cancer research.

[19]  J. Licht,et al.  Translocations of the RARα gene in acute promyelocytic leukemia , 2001, Oncogene.

[20]  P. Pandolfi.  Transcription therapy for cancer , 2001, Oncogene.

[21]  P. Marks,et al.  Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors , 1999, Nature.

[22]  Sandy D. Westerheide,et al.  The p65 (RelA) Subunit of NF-κB Interacts with the Histone Deacetylase (HDAC) Corepressors HDAC1 and HDAC2 To Negatively Regulate Gene Expression , 2001, Molecular and Cellular Biology.

[23]  V. Kiermer,et al.  The emerging role of class II histone deacetylases. , 2001, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[24]  V. L. Greenberg,et al.  Histone deacetylase inhibitors promote apoptosis and differential cell cycle arrest in anaplastic thyroid cancer cells. , 2001, Thyroid : official journal of the American Thyroid Association.

[25]  S. Pavey,et al.  Up-regulation of p21(WAF1/CIP1) by histone deacetylase inhibitors reduces their cytotoxicity. , 2001, Molecular pharmacology.

[26]  F. Marincola,et al.  Sequential 5-Aza-2′-deoxycytidine-Depsipeptide FR901228 Treatment Induces Apoptosis Preferentially in Cancer Cells and Facilitates Their Recognition by Cytolytic T Lymphocytes Specific for NY-ESO-1 , 2001, Journal of immunotherapy.

[27]  B. Chauffert,et al.  Cancer cell sensitization to Fas-mediated apoptosis by sodium butyrate , 1998, Cell Death and Differentiation.

[28]  W. D. Cress,et al.  Histone deacetylases, transcriptional control, and cancer , 2000, Journal of cellular physiology.

[29]  S. Kyo,et al.  Telomerase activation by histone deacetylase inhibitor in normal cells. , 2001, Nucleic acids research.

[30]  L. Pillus,et al.  Modifying chromatin and concepts of cancer. , 1999, Current opinion in genetics & development.

[31]  Keith D Robertson,et al.  DNA methylation, methyltransferases, and cancer , 2001, Oncogene.

[32]  D. C. Henckel,et al.  Case report. , 1995, Journal.

[33]  P. Pandolfi,et al.  Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. , 1998, Journal of the National Cancer Institute.

[34]  F. Behm,et al.  Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN , 2000, Nature Medicine.

[35]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[36]  R. Goodman,et al.  CBP/p300 in cell growth, transformation, and development. , 2000, Genes & development.

[37]  R. Greil,et al.  Inhibition of histone deacetylase activity enhances Fas receptor-mediated apoptosis in leukemic lymphoblasts , 2001, Cell Death and Differentiation.

[38]  Yang Shi,et al.  The Human Factors YY1 and LSF Repress the Human Immunodeficiency Virus Type 1 Long Terminal Repeat via Recruitment of Histone Deacetylase 1 , 2000, Journal of Virology.

[39]  S. Alkan,et al.  Histone deacetylase inhibitors induce caspase‐dependent apoptosis and downregulation of daxx in acute promyelocytic leukaemia with t(15;17) , 2001, British journal of haematology.

[40]  T. Jacks,et al.  The retinoblastoma gene family in differentiation and development , 1999, Oncogene.

[41]  M. Breuning,et al.  Conjunction dysfunction: CBP/p300 in human disease. , 1998, Trends in genetics : TIG.

[42]  A. Leutz,et al.  Chromatin remodeling in development and differentiation. , 2001, Current opinion in genetics & development.

[43]  J. Licht.  AML1 and the AML1-ETO fusion protein in the pathogenesis of t(8;21) AML , 2001, Oncogene.

[44]  B. Johansson,et al.  Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13). , 2001, Human molecular genetics.

[45]  P G Pelicci,et al.  Histone deacetylase-targeted treatment restores retinoic acid signaling and differentiation in acute myeloid leukemia. , 2001, Cancer research.

[46]  N. Rosen,et al.  The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells. , 2001, Cancer research.

[47]  D. Bernhard,et al.  Suberoylanilide hydroxamic acid (SAHA) overcomes multidrug resistance and induces cell death in P‐glycoprotein‐expressing cells , 2002, International journal of cancer.

[48]  T. Naoe,et al.  Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia: a new approach to anti-leukemia therapy , 1999, Leukemia.

[49]  P. Marks,et al.  A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[50]  G. Almouzni,et al.  The ins and outs of nucleosome assembly. , 2001, Current opinion in genetics & development.

[51]  S. Schreiber,et al.  Synthesis of 7200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin. , 2001, Organic letters.

[52]  M. Jung,et al.  Inhibitors of histone deacetylase as new anticancer agents. , 2001, Current medicinal chemistry.

[53]  Delin Chen,et al.  Deacetylation of p53 modulates its effect on cell growth and apoptosis , 2000, Nature.

[54]  Peter L. Jones,et al.  DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters , 2000, Nature Genetics.

[55]  W. Gerald,et al.  Inactivation of the apoptosis effector Apaf-1 in malignant melanoma , 2001, Nature.

[56]  T. Heinzel,et al.  Histone deacetylase as a therapeutic target , 2001, Trends in Endocrinology & Metabolism.

[57]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[58]  V. Richon,et al.  Histone deacetylase inhibitors as new cancer drugs , 2001, Current opinion in oncology.

[59]  L. Grochow,et al.  A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[60]  Eun-Joung Moon,et al.  Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes , 2001, Nature Medicine.

[61]  J. Harbour,et al.  Chromatin remodeling and Rb activity. , 2000, Current opinion in cell biology.

[62]  Delin Chen,et al.  Negative Control of p53 by Sir2α Promotes Cell Survival under Stress , 2001, Cell.

[63]  T. Kouzarides.  Histone acetylases and deacetylases in cell proliferation. , 1999, Current opinion in genetics & development.

[64]  M. Yoshida,et al.  Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[65]  J. Mariadason,et al.  Genetic reprogramming in pathways of colonic cell maturation induced by short chain fatty acids: comparison with trichostatin A, sulindac, and curcumin and implications for chemoprevention of colon cancer. , 2000, Cancer research.

[66]  M. Ptashne,et al.  Activation of gene expression by small molecule transcription factors. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[67]  E. Wintersberger,et al.  Histone Deacetylase 1 Can Repress Transcription by Binding to Sp1 , 1999, Molecular and Cellular Biology.

[68]  C. Allis,et al.  Translating the Histone Code , 2001, Science.

[69]  S. Grant,et al.  Evidence of a functional role for the cyclin-dependent kinase-inhibitor p21WAF1/CIP1/MDA6 in promoting differentiation and preventing mitochondrial dysfunction and apoptosis induced by sodium butyrate in human myelomonocytic leukemia cells (U937). , 2001, International journal of oncology.

[70]  M. Guenther,et al.  Histone Deacetylase Is a Direct Target of Valproic Acid, a Potent Anticonvulsant, Mood Stabilizer, and Teratogen* , 2001, The Journal of Biological Chemistry.

[71]  J. Herman,et al.  Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours , 2002, The Journal of pathology.

[72]  R A Rifkind,et al.  Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. , 2000, Cancer research.

[73]  Yung-Hyun Choi,et al.  Sensing of Ionizing Radiation-induced DNA Damage by ATM through Interaction with Histone Deacetylase* , 1999, The Journal of Biological Chemistry.

[74]  T. Tsuruo,et al.  Cyclic hydroxamic-acid-containing peptide 31, a potent synthetic histone deacetylase inhibitor with antitumor activity. , 2001, Cancer research.

[75]  M. Okuhara,et al.  FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity. , 1994, The Journal of antibiotics.

[76]  E. Sausville,et al.  P21-dependent G 1 arrest with downregulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228 , 2000, British Journal of Cancer.

[77]  Ping Zhu,et al.  Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells , 2001, The EMBO journal.

[78]  T. Tomasi,et al.  Activation of MHC Class I, II, and CD40 Gene Expression by Histone Deacetylase Inhibitors1 , 2000, The Journal of Immunology.

[79]  I. Kawamura,et al.  FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice. , 1994, The Journal of antibiotics.

[80]  P. Marks,et al.  Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. , 2000, Journal of the National Cancer Institute.

[81]  A. Skoultchi,et al.  Coordinating cell proliferation and differentiation. , 2001, Current opinion in genetics & development.

[82]  C C Case,et al.  Regulation of an Endogenous Locus Using a Panel of Designed Zinc Finger Proteins Targeted to Accessible Chromatin Regions , 2001, The Journal of Biological Chemistry.

[83]  R. Marmorstein,et al.  Histone acetyltransferases: function, structure, and catalysis. , 2001, Current opinion in genetics & development.

[84]  Carlos Caldas,et al.  Mutations truncating the EP300 acetylase in human cancers , 2000, Nature Genetics.

[85]  P. Liberator,et al.  Histone deacetylase: a target for antiproliferative and antiprotozoal agents. , 2001, Current medicinal chemistry.

[86]  W. Wilson,et al.  Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report. , 2001, Blood.

[87]  U. Weidle,et al.  Inhibition of histone deacetylases: a new strategy to target epigenetic modifications for anticancer treatment. , 2000, Anticancer research.

[88]  Dana M. King,et al.  Mechanisms of transcriptional repression by the t(8;21)-, t(12;21)-, and inv(16)-encoded fusion proteins , 2001, Cancer Chemotherapy and Pharmacology.

[89]  R C Coombes,et al.  Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[90]  P. Marks,et al.  Hybrid polar histone deacetylase inhibitor induces apoptosis and CD95/CD95 ligand expression in human neuroblastoma. , 1999, Cancer research.

[91]  T. Tamura,et al.  In vivo complex formation of PU.1 with HDAC1 associated with PU.1-mediated transcriptional repression , 2001, Oncogene.

[92]  J. Herman,et al.  DNA methylation, chromatin inheritance, and cancer , 2001, Oncogene.

[93]  J. Doly,et al.  Inhibition of Histone Deacetylation Induces Constitutive Derepression of the Beta Interferon Promoter and Confers Antiviral Activity , 2001, Journal of Virology.

[94]  V. L. Greenberg,et al.  Butyrate alters the expression and activity of cell cycle components in anaplastic thyroid carcinoma cells. , 2001, Thyroid : official journal of the American Thyroid Association.

[95]  深山 正久.  p300 Gene Alterations in Colorectal and Gastric Carcinomas , 1997 .

[96]  R. Evans,et al.  Transcriptional regulation in acute promyelocytic leukemia , 2001, Oncogene.

[97]  K. Kandror,et al.  Tip60 and HDAC7 Interact with the Endothelin Receptor A and May Be Involved in Downstream Signaling* , 2001, The Journal of Biological Chemistry.

[98]  G. Bae,et al.  Apicidin, a Histone Deacetylase Inhibitor, Induces Apoptosis and Fas/Fas Ligand Expression in Human Acute Promyelocytic Leukemia Cells* , 2002, The Journal of Biological Chemistry.

[99]  J. Trapani,et al.  Perforin-dependent nuclear entry of granzyme B precedes apoptosis, and is not a consequence of nuclear membrane dysfunction , 1998, Cell Death and Differentiation.

[100]  T. Tsuruo,et al.  A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[101]  J C Reed,et al.  Dysregulation of apoptosis in cancer. , 1998, The cancer journal from Scientific American.

[102]  T. Kouzarides,et al.  Dnmt3a binds deacetylases and is recruited by a sequence‐specific repressor to silence transcription , 2001, The EMBO journal.

[103]  R. Weinberg,et al.  hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase , 2001, Cell.

[104]  L. Grochow,et al.  A Phase I clinical and pharmacological evaluation of sodium phenylbutyrate on an 120-h infusion schedule. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[105]  Yufang Shi,et al.  Fungal metabolite FR901228 inhibits c-Myc and Fas ligand expression , 1998, Oncogene.

[106]  T. Naoe,et al.  In vivo Effects of a Histone Deacetylase Inhibitor, FK228, on Human Acute Promyelocytic Leukemia in NOD/Shi‐scid/scid Mice , 2001, Japanese journal of cancer research : Gann.

[107]  K. Naka,et al.  Effect of trichostatin A on cell growth and expression of cell cycle‐ and apoptosis‐related molecules in human gastric and oral carcinoma cell lines , 2000, International journal of cancer.

[108]  G. Kammer,et al.  Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon-γ gene and protein expression in lupus T cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[109]  Paul Tempst,et al.  MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex , 1999, Nature Genetics.

[110]  P. Marks,et al.  Histone deacetylases and cancer: causes and therapies , 2001, Nature Reviews Cancer.

[111]  Eric Verdin,et al.  Duration of Nuclear NF-κB Action Regulated by Reversible Acetylation , 2001, Science.

[112]  P. Marks,et al.  The histone deacetylase inhibitor, CBHA, inhibits growth of human neuroblastoma xenografts in vivo, alone and synergistically with all-trans retinoic acid. , 2001, Cancer research.

[113]  E. Olson,et al.  Control of muscle development by dueling HATs and HDACs. , 2001, Current opinion in genetics & development.

[114]  寺尾 泰久.  Sodium butyrate induces growth arrest and senescence-like phenotypes in gynecologic cancer cells , 2002 .

[115]  L. Kedes,et al.  Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis. , 2001, Molecular cell.

[116]  J. Herman,et al.  Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer , 1999, Nature Genetics.

[117]  L. Guarente,et al.  Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase , 2000, Nature.

[118]  A. Verdel,et al.  Functional significance of histone deacetylase diversity. , 2001, Current opinion in genetics & development.

[119]  D. Sterner,et al.  Acetylation of Histones and Transcription-Related Factors , 2000, Microbiology and Molecular Biology Reviews.

[120]  S. Grant,et al.  Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53 , 1999, Oncogene.

[121]  M. Grunstein,et al.  25 years after the nucleosome model: chromatin modifications. , 2000, Trends in biochemical sciences.

[122]  D. Bernhard,et al.  Apoptosis induced by the histone deacetylase inhibitor sodium butyrate in human leukemic lymphoblasts , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.