Histone deacetylase inhibitors as anticancer drugs

International Journal of Molecular Sciences

Volumn 18, Issue 7, 2017, Pages

  Eckschlager, Tomas ^a   Plch, Johana ^a   Stiborova, Marie ^b   Hrabeta, Jan ^a  

^a UNIVERSITY HOSPITAL MOTOL   (Czech Republic)

^b CHARLES UNIVERSITY   (Czech Republic)

Author keywords

Anti angiogenic effect; Apoptosis; Autophagy; Cancer; Cell cycle arrest; Drug combinations; Histone deacetylase inhibitors; Histone deacetylases

Indexed keywords

ABEXINOSTAT; BENZAMIDE; CATENIN; ERYTHROID KRUPPEL LIKE FACTOR; GIVINOSTAT; HISTONE ACETYLTRANSFERASE; HISTONE DEACETYLASE INHIBITOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MOCETINOSTAT; MYC PROTEIN; MYOD PROTEIN; NICOTINAMIDE; PANOBINOSTAT; PRACINOSTAT; RESMINOSTAT; RICOLINOSTAT; ROMIDEPSIN; SIRTUIN 1; SIRTUIN 2; STAT3 PROTEIN; TACEDINALINE; TATA BINDING PROTEIN; TETRAPEPTIDE; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR GATA 1; TRANSCRIPTION FACTOR RUNX3; TRICHOSTATIN A; UNTRANSLATED RNA; VASCULOTROPIN; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT;

ACETYLATION; ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; AUTOPHAGY; CELL CYCLE ARREST; DEACETYLATION; DNA REPAIR; ENZYME PHOSPHORYLATION; GENE OVEREXPRESSION; HUMAN; MULTIPLE MYELOMA; NONHUMAN; REVIEW; RNA SPLICING; SIGNAL TRANSDUCTION; T CELL LYMPHOMA; ANIMAL; CELL CYCLE CHECKPOINT; CLINICAL TRIAL (TOPIC); DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; IMMUNOMODULATION; PRECLINICAL STUDY;

ACETYLATION; ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; AUTOPHAGY; CELL CYCLE CHECKPOINTS; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HISTONE DEACETYLASE INHIBITORS; HUMANS; IMMUNOMODULATION; SIGNAL TRANSDUCTION;

EID: 85021647638     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms18071414     Document Type: Review

References (181)

1. Li, G.; Margueron, R.; Hu, G.; Stokes, D.; Wang, Y.H.; Reinberg, D. Highly compacted chromatin formed in vitro reflects the dynamics of transcription activation in vivo. Mol. Cell 2010, 38, 41–53.
2. Perri, F.; Longo, F.; Giuliano, M.; Sabbatino, F.; Favia, G.; Ionna, F.; Addeo, R.; Scarpati, G.D.V.; Di Lorenzo, G.; Pisconti, S. Epigenetic control of gene expression: Potential implications for cancer treatment. Crit. Rev. Oncol. Hematol. 2017, 111, 166–172.
3. Haberland, M.; Montgomery, R.L.; Olson, E.N. The many roles of histone deacetylases in development and physiology: Implications for disease and therapy. Nat. Rev. Genet. 2009, 10, 32–42.
4. Yang, X.-J.; Seto, E. The Rpd3/Hda1 family of lysine deacetylases: From bacteria and yeast to mice and men. Nat. Rev. Mol. Cell Biol. 2008, 9, 206–218.
5. Yan, W.; Herman, J.G.; Guo, M. Epigenome-based personalized medicine in human cancer. Epigenomics 2015, 8, 119–133.
6. Halkidou, K.; Gaughan, L.; Cook, S.; Leung, H.Y.; Neal, D.E.; Robson, C.N. Upregulation and nuclear recruitment of HDACl in hormone refractory prostate cancer. Prostate 2004, 59, 177–189.
7. Choi, J.-H.; Kwon, H.J.; Yoon, B.-I.; Kim, J.-H.; Han, S.U.; Joo, H.J.; Kim, D.-Y. Expression profile of histone deacetylase 1 in gastric cancer tissues. Jpn. J. Cancer Res. 2001, 92, 1300–1304.
8. Zhang, Z.; Yamashita, H.; Toyama, T.; Sugiura, H.; Ando, Y.; Mita, K.; Hamaguchi, M.; Hara, Y.; Kobayashi, S.; Iwase, H. Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast. Breast Cancer Res. Treat. 2005, 94, 11–16.
9. Song, J.; Noh, J.H.; Lee, J.H.; Eun, J.W.; Ahn, Y.M.; Kim, S.Y.; Lee, S.H.; Park, W.S.; Yoo, N.J.; Lee, J.Y., et al. Increased expression of histone deacetylase 2 is found in human gastric cancer. APMIS 2005, 113, 264–8.
10. Zhu, P.; Martin, E.; Mengwasser, J.; Schlag, P.; Janssen, K.P.; Göttlicher, M. Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. Cancer Cell 2004, 5, 455–463.
11. Wilson, A.J.; Byun, D.S.; Popova, N.; Murray, L.B.; L’Italien, K.; Sowa, Y.; Arango, D.; Velcich, A.; Augenlicht, L.H.; Mariadason, J.M. Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J. Biol. Chem. 2006, 281, 13548–13558.
12. Bolden, J.E.; Peart, M.M.J.; Johnstone, R.R.W. Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 2006, 5, 769–784.
13. Nakagawa, M.; Oda, Y.; Eguchi, T.; Aishima, S.-I.; Yao, T.; Hosoi, F.; Basaki, Y.; Ono, M.; Kuwano, M.; Tanaka, M., et al. Expression profile of class I histone deacetylases in human cancer tissues. Oncol. Rep. 2007, 18, 769–774.
14. Oehme, I.; Deubzer, H.E.; Wegener, D.; Pickert, D.; Linke, J.P.; Hero, B.; Kopp-Schneider, A.; Westermann, F.; Ulrich, S.M.; Von Deimling, A., et al. Histone deacetylase 8 in neuroblastoma tumorigenesis. Clin. Cancer Res. 2009, 15, 91–99.
15. Hayashi, A.; Horiuchi, A.; Kikuchi, N.; Hayashi, T.; Fuseya, C.; Suzuki, A.; Konishi, I.; Shiozawa, T. Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E-cadherin. Int. J. Cancer 2010, 127, 1332–1346.
16. Roth, S.Y.; Allis, C.D. Histone acetylation and chromatin assembly: A single escort, multiple dances? Cell 1996, 87, 5–8.
17. Kazanets, A.; Shorstova, T.; Hilmi, K.; Marques, M.; Witcher, M. Epigenetic silencing of tumor suppressor genes: Paradigms, puzzles, and potential. Biochim. Biophys. Acta Rev. Cancer 2016, 1865, 275–288.
18. Spange, S.; Wagner, T.; Heinzel, T.; Krämer, O.H. Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Int. J. Biochem. Cell Biol. 2009, 41, 185–198.
19. Hull, E.E.; Montgomery, M.R.; Leyva, K.J. HDAC Inhibitors as epigenetic regulators of the immune system: Impacts on cancer therapy and inflammatory diseases. BioMed Res. Int. 2016, 2016, 8797206.
20. Tang, J.; Yan, H.; Zhuang, S. Histone deacetylases as targets for treatment of multiple diseases. Clin. Sci. 2013, 124, 651–662.
21. Finnin, M.S.; Donigian, J.R.; Cohen, A.; Richon, V.M.; Rifkind, R.A.; Marks, P.A.; Breslow, R.; Pavletich, N.P. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 1999, 401, 188–193.
22. Trapp, J.; Jung, M. The role of NAD+ dependent histone deacetylases (sirtuins) in ageing. Curr. Drug Targets 2006, 7, 1553–1560.
23. Yang, X.J.; Seto, E. Lysine acetylation: Codified crosstalk with other posttranslational modifications. Mol. Cell 2008, 31, 449–461.
24. Karagianni, P.; Wong, J. HDAC3: Taking the SMRT-N-CoRrect road to repression. Oncogene 2007, 26, 5439–5449.
25. Li, J.; Wang, J.; Wang, J.; Nawaz, Z.; Liu, J.M.; Qin, J.; Wong, J. Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3. EMBO J. 2000, 19, 4342–4350.
26. Lee, K.K.; Workman, J.L. Histone acetyltransferase complexes: One size doesn’t fit all. Nat. Rev. Mol. Cell Biol. 2007, 8, 284–295.
27. Mariadason, J.M.; Corner, G.A.; Augenlicht, L.H. 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. Cancer Res. 2000, 60, 4561–4572.
28. Ceccacci, E.; Minucci, S. Inhibition of histone deacetylases in cancer therapy: Lessons from leukaemia. Br. J. Cancer 2016, 114, 605–611.
29. Furumai, R.; Matsuyama, A.; Kobashi, N.; Lee, K.H.; Nishiyama, M.; Nakajima, H.; Tanaka, A.; Komatsu, Y.; Nishino, N.; Yoshida, M., et al. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res. 2002, 62, 4916–4921.
30. Lavu, S.; Boss, O.; Elliott, P.J.; Lambert, P.D. Sirtuins—Novel therapeutic targets to treat age-associated diseases. Nat. Rev. Drug Discov. 2008, 7, 841–853.
31. Falkenberg, K.J.; Johnstone, R.W. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat. Rev. Drug Discov. 2014, 13, 673–691.
32. Valente, S.; Mai, A. Small-molecule inhibitors of histone deacetylase for the treatment of cancer and non-cancer diseases: A patent review (2011–2013). Expert Opin. Ther. Pat. 2014, 24, 401–415.
33. West, A.C.; Johnstone, R.W. New and emerging HDAC inhibitors for cancer treatment. J. Clin. Investig. 2014, 124, 30–39.
34. Dokmanovic, M.; Marks, P.A. Prospects: Histone deacetylase inhibitors. J. Cell Biochem. 2005, 96, 293–304.
35. Rasheed, W.K.; Johnstone, R.W.; Prince, H.M. Histone deacetylase inhibitors in cancer therapy. Expert Opin Investig. Drugs 2007, 16, 659–678.
36. Xu, W.S.; Parmigiani, R.B.; Marks, P.A. Histone deacetylase inhibitors: Molecular mechanisms of action. Oncogene 2007, 26, 5541–5552.
37. Stiborova, M.; Eckschlager, T.; Poljakova, J.; Hrabeta, J.; Adam, V.; Kizek, R.; Frei, E. The synergistic effects of DNA-targeted chemotherapeutics and histone deacetylase inhibitors as therapeutic strategies for cancer treatment. Curr. Med. Chem. 2012, 19, 4218–4238.
38. Dawson, M.A.; Kouzarides, T. Cancer epigenetics: From mechanism to therapy. Cell 2012, 150, 12–27.
39. Kretsovali, A.; Hadjimichael, C.; Charmpilas, N. Histone deacetylase inhibitors in cell pluripotency, differentiation, and reprogramming. Stem Cells Int. 2012, 2012, 184154.
40. Chen, C.L.; Sung, J.; Cohen, M.; Chowdhury, W.H.; Sachs, M.D.; Li, Y.; Lakshmanan, Y.; Yung, B.Y.; Lupold, S.E.; Rodriguez, R. Valproic acid inhibits invasiveness in bladder cancer but not in prostate cancer cells. J. Pharmacol. Exp. Ther. 2006, 319, 533–542.
41. Stockhausen, M.-T.; Sjölund, J.; Manetopoulos, C.; Axelson, H. Effects of the histone deacetylase inhibitor valproic acid on Notch signalling in human neuroblastoma cells. Br. J. Cancer 2005, 92, 751–759.
42. Vrana, J.A.; Decker, R.H.; Johnson, C.R.; Wang, Z.; Jarvis, W.D.; Richon, V.M.; Ehinger, M.; Fisher, P.B.; Grant, S. 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. Oncogene 1999, 18, 7016–7025.
43. Richon, V.M.; Sandhoff, T.W.; Rifkind, R.A.; Marks, P.A. Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Proc. Natl. Acad. Sci. USA 2000, 97, 10014–10019.
44. Sandor, V.; Senderowicz, A. Mertins, S.; Sackett, D.; Sausville, E.; Blagosklonny, M.V.; Bates, S.E. P21-dependent G1arrest with downregulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228. Br. J. Cancer 2000, 83, 817–825.
45. Ocker, M.; Schneider-Stock, R. Histone deacetylase inhibitors: Signalling towards p21cip1/waf1. Int. J. Biochem. Cell Biol. 2007, 39, 1367–1374.
46. Gius, D.; Cui, H.; Bradbury, C.M.; Cook, J.; Smart, D.D.K.; Zhao, S.; Young, L.; Brandenburg, S.A.; Hu, Y.; Bisht, K.S., et al. Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach. Cancer Cell 2004, 6, 361–371.
47. Zhao, Y.; Lu, S.; Wu, L.; Chai, G.; Wang, H.; Chen, Y.; Sun, J.; Yu, Y.; Zhou, W.; Zheng, Q., et al. Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21(Waf1/Cip1). Mol. Cell. Biol. 2006, 26, 2782–2790.
48. Tang, Y.; Zhao, W.; Chen, Y.; Zhao, Y.; Gu, W. Acetylation is indispensable for p53 Activation. Cell 2008, 133, 612–626.
49. Mahyar-Roemer, M.; Roemer, K. p21 Waf1/Cip1 can protect human colon carcinoma cells against p53-dependent and p53-independent apoptosis induced by natural chemopreventive and therapeutic agents. Oncogene 2001, 20, 3387–3398.
50. Suzuki, T.; Yokozaki, H.; Kuniyasu, H.; Hayashi, K.; Naka, K.; Ono, S.; Ishikawa, T.; Tahara, E.; Yasui, W. Effect of trichostatin A on cell growth and expression of cell cycle- and apoptosis-related molecules in human gastric and oral carcinoma cell lines. Int. J. Cancer 2000, 88, 992–997.
51. Qiu, L.; Burgess, A.; Fairlie, D.P.; Leonard, H.; Parsons, P.G.; Gabrielli, B.G. Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells. Mol. Biol. Cell 2000, 11, 2069–2083.
52. Cecconi, D.; Donadelli, M.; Pozza, E.D.; Rinalducci, S.; Zolla, L.; Scupoli, M.T.; Righetti, P.G.; Scarpa, A.; Palmieri, M. Synergistic effect of trichostatin A and 5-aza-2′-deoxycytidine on growth inhibition of pancreatic endocrine tumour cell lines: A proteomic study. Proteomics 2009, 9, 1952–1966.
53. Gu, W.; Roeder, R.G. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 1997, 90, 595–606.
54. Li, Q.L.; Ito, K.; Sakakura, C.; Fukamachi, H.; Inoue, K.I.; Chi, X.Z.; Lee, K.Y.; Nomura, S.; Lee, C.W.; Han, S.B., et al. Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 2002, 109, 113–124.
55. Walton, T.J.; Li, G.; Seth, R.; McArdle, S.E.; Bishop, M.C.; Rees, R.C. DNA demethylation and histone deacetylation inhibition co-operate to re-express estrogen receptor β and induce apoptosis in prostate cancer cell-lines. Prostate 2008, 68, 210–222.
56. Kim, H.J.; Bae, S.C. Histone deacetylase inhibitors: Molecular mechanisms of action and clinical trials as anti-cancer drugs. Am. J. Transl. Res. 2011, 3, 166–179.
57. Minucci, S.; Pelicci, P.G. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat. Rev. Cancer 2006, 6, 38–51.
58. Miller, C.P.; Singh, M.M.; Rivera-Del Valle, N.; Manton, C.A.; Chandra, J. Therapeutic strategies to enhance the anticancer efficacy of histone deacetylase inhibitors. J. Biomed. Biotechnol. 2011, 2011, 514261.
59. Fulda, S. Modulation of TRAIL-induced apoptosis by HDAC inhibitors. Curr. Cancer Drug Targets 2008, 8, 132–140.
60. Kwon, S.H.; Ahn, S.H.; Kim, Y.K.; Bae, G.U.; Yoon, J.W.; Hong, S.; Lee, H.Y.; Lee, Y.W.; Lee, H.W.; Han, J.W. Apicidin, a Histone Deacetylase Inhibitor, induces apoptosis and Fas/Fas ligand expression in human acute promyelocytic leukemia cells. J. Biol. Chem. 2002, 277, 2073–2080.
61. Nebbioso, A.; Clarke, N.; Voltz, E.; Germain, E.; Ambrosino, C.; Bontempo, P.; Alvarez, R.; Schiavone, E.M.; Ferrara, F.; Bresciani, F., et al. Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat. Med. 2005, 11, 77–84.
62. Insinga, A.; Monestiroli, S.; Ronzoni, S.; Gelmetti, V.; Marchesi, F.; Viale, A.; Altucci, L.; Nervi, C.; Minucci, S.; Pelicci, P.G. Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway. Nat. Med. 2005, 11, 71–76.
63. Ruefli, A.A.; Ausserlechner, M.J.; Bernhard, D.; Sutton, V.R.; Tainton, K.M.; Kofler, R.; Smyth, M.J.; Johnstone, R.W. 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. 2001, 98, 10833–10838.
64. Zhao, Y.; Tan, J.; Zhuang, L.; Jiang, X.; Liu, E.T.; Yu, Q. Inhibitors of histone deacetylases target the Rb-E2F1 pathway for apoptosis induction through activation of proapoptotic protein Bim. Proc. Natl. Acad. Sci. USA 2005, 102, 16090–16095.
65. Yuan, P.X.; Huang, L.D.; Jiang, Y.M.; Gutkind, J.S.; Manji, H.K.; Chen, G. The Mood Stabilizer Valproic Acid Activates Mitogen-activated Protein Kinases and Promotes Neurite Growth. J. Biol. Chem. 2001, 276, 31674–31683.
66. Gao, S.; Mobley, A.; Miller, C.; Boklan, J.; Chandra, J. Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells. Leuk. Res. 2008, 32, 771–780.
67. Rosato, R.R.; Almenara, J.A.; Grant, S. 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. 2003, 63, 3637–3645.
68. Butler, L.M.; Zhou, X.; Xu, W.-S.; Scher, H.I.; Rifkind, R.A.; Marks, P.A.; Richon, V.M. The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Proc. Natl. Acad. Sci. USA 2002, 99, 11700–11705.
69. Lincoln, D.T.; Ali Emadi, E.M.; Tonissen, K.F.; Clarke, F.M. The thioredoxin-thioredoxin reductase system: Over-expression in human cancer. Anticancer Res. 2003, 23, 2425–2433.
70. Shao, L.E.; Diccianni, M.B.; Tanaka, T.; Gribi, R.; Yu, A.L.; Pullen, J.D.; Camitta, B.M.; Yu, J. Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its therapeutic implication. Cancer Res. 2001, 61, 7333–7338.
71. Cipro, Š.; Hřebačková, J.; Hraběta, J.; Poljaková, J.; Eckschlager, T. Valproic acid overcomes hypoxia-induced resistance to apoptosis. Oncol. Rep. 2012, 27, 1219–1226.
72. Jeong, J.W.; Bae, M.K.; Ahn, M.Y.; Kim, S.H.; Sohn, T.K.; Bae, M.H.; Yoo, M.A.; Song, E.J.; Lee, K.J.; Kim, K.W. Regulation and destabilization of HIF-1α by ARD1-mediated acetylation. Cell 2002, 111, 709–720.
73. Zhang, J.; Zhong, Q. Histone deacetylase inhibitors and cell death. Cell. Mol. Life Sci. 2014, 3885–3901.
74. Brunet, A.; Sweeney, L.B.; Sturgill, J.F.; Chua, K.F.; Greer, P.L.; Lin, Y.; Tran, H.; Ross, S.E.; Mostoslavsky, R.; Cohen, H.Y., et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 2004, 303, 2011–2015.
75. Cao, D.J.; Wang, Z. V; Battiprolu, P.K.; Jiang, N.; Morales, C.R.; Kong, Y.; Rothermel, B.A.; Gillette, T.G.; Hill, J.A. Histone deacetylase (HDAC) inhibitors attenuate cardiac hypertrophy by suppressing autophagy. Proc. Natl. Acad. Sci. USA 2011, 108, 4123–4128.
76. Oh, M.; Choi, I.K.; Kwon, H.J. Inhibition of histone deacetylase1 induces autophagy. Biochem. Biophys. Res. Commun. 2008, 369, 1179–1183.
77. Oehme, I.; Linke, J.-P.; Böck, B.C.; Milde, T.; Lodrini, M.; Hartenstein, B.; Wiegand, I.; Eckert, C.; Roth, W.; Kool, M., et al. Histone deacetylase 10 promotes autophagy-mediated cell survival. Proc. Natl. Acad. Sci. USA 2013, 110, E2592–E2601.
78. Lee, I.H.; Cao, L.; Mostoslavsky, R.; Lombard, D.B.; Liu, J.; Bruns, N.E.; Tsokos, M.; Alt, F.W.; Finkel, T. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc. Natl. Acad. Sci. USA 2008, 105, 3374–3379.
79. Zhang, J.; Ng, S.; Wang, J.; Zhou, J.; Tan, S.H.; Yang, N.; Lin, Q.; Xia, D.; Shen, H.M. Histone deacetylase inhibitors induce autophagy through FOXO1-dependent pathways. Autophagy 2015, 11, 629–642.
80. Liu, Y.L.; Yang, P.M.; Shun, C.T.; Wu, M.S.; Weng, J.R.; Chen, C.C. Autophagy potentiates the anti-cancer effects of the histone deacetylase inhibitors in hepatocellular carcinoma. Autophagy 2010, 6, 1057–1065.
81. Hrzenjak, A.; Kremser, M.L.; Strohmeier, B.; Moinfar, F.; Zatloukal, K.; Denk, H. SAHA induces caspase-independent, autophagic cell death of endometrial stromal sarcoma cells by influencing the mTOR pathway. J. Pathol. 2008, 216, 495–504.
82. Fröhlich, L.F.; Mrakovcic, M.; Smole, C.; Zatloukal, K. Molecular mechanism leading to SAHA-induced autophagy in tumor cells: Evidence for a p53-dependent pathway. Cancer Cell Int. 2016, 16, 68.
83. Gammoh, N.; Lam, D.; Puente, C.; Ganley, I.; Marks, P.A.; Jiang, X. Role of autophagy in histone deacetylase inhibitor-induced apoptotic and nonapoptotic cell death. Proc. Natl. Acad. Sci. USA 2012, 109, 6561–6565.
84. Li, J.; Liu, R.; Lei, Y.; Wang, K.; Lau, Q.C.; Xie, N.; Zhou, S.; Nie, C.; Chen, L.; Wei, Y., et al. Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in jurkat T-leukemia cells. Autophagy 2010, 6, 711–724.
85. Autophagy, B.; Shulak, L.; Beljanski, V.; Chiang, C.; Dutta, M.; Van Grevenynghe, J.; Belgnaoui, S.M.; Nguyên, L.; Di Lenardo, T.; Semmes, O.J., et al. Histone deacetylase inhibitors potentiate vesicular stomatitis virus oncolysis in prostate cancer cells by modulating NF-κB-dependent autophagy. J. Virol. 2014, 88, 2927–2940.
86. Park, M.A.; Reinehr, R.; Haussinger, D.; Voelkel-Johnson, C.; Ogretmen, B.; Yacoub, A.; Grant, S.; Dent, P. Sorafenib activates CD95 and promotes autophagy and cell death via Src family kinases in gastrointestinal tumor cells. Mol. Cancer Ther. 2010, 9, 2220–2231.
87. Chiao, M.T.; Cheng, W.Y.; Yang, Y.C.; Shen, C.C.; Ko, J.L. Suberoylanilide hydroxamic acid (SAHA) causes tumor growth slowdown and triggers autophagy in glioblastoma stem cells. Autophagy 2013, 9, 1509–1526.
88. Brest, P.; Lassalle, S.; Hofman, V.; Bordone, O.; Tanga, V.G.; Bonnetaud, C.; Moreilhon, C.; Rios, G.; Santini, J.; Barbry, P., et al. MiR-129–5p is required for histone deacetylase inhibitor-induced cell death in thyroid cancer cells. Endocr. Relat. Cancer 2011, 18, 711–719.
89. Cho, J.H.; Dimri, M.; Dimri, G.P. MicroRNA-31 is a transcriptional target of histone deacetylase inhibitors and a regulator of cellular senescence. J. Biol. Chem. 2015, 290, 10555–10567.
90. Adams, C.M.; Hiebert, S.W.; Eischen, C.M. Myc Induces miRNA-mediated apoptosis in response to HDAC inhibition in hematologic malignancies. Cancer Res. 2016, 76, 736–748.
91. Wada, T.; Kikuchi, J.; Furukawa, Y. Histone deacetylase 1 enhances microRNA processing via deacetylation of DGCR8. EMBO Rep. 2012, 13, 142–149.
92. Noonan, E.J.; Place, R.F.; Pookot, D.; Basak, S.; Whitson, J.M.; Hirata, H.; Giardina, C.; Dahiya, R. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene 2009, 28, 1714–1724.
93. Moran, V.A.; Perera, R.J.; Khalil, A.M. Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res. 2012, 40, 6391–6400.
94. Brockdorff, N. Noncoding RNA and Polycomb recruitment. RNA 2013, 19, 429–442.
95. Yang, H.; Zhong, Y.; Xie, H.; Lai, X.; Xu, M.; Nie, Y.; Liu, S.; Wan, Y.J.Y. Induction of the liver cancer-down-regulated long noncoding RNA uc002mbe.2 mediates trichostatin-induced apoptosis of liver cancer cells. Biochem. Pharmacol. 2013, 85, 1761–1769.
96. Gibb, E.A.; Brown, C.J.; Lam, W.L. The functional role of long non-coding RNA in human carcinomas. Mol. Cancer 2011, 10, 38.
97. Salvador, M.A.; Wicinski, J.; Cabaud, O.; Toiron, Y.; Finetti, P.; Josselin, E.; Lelièvre, H.; Kraus-Berthier, L.; Depil, S.; Bertucci, F., et al. The histone deacetylase inhibitor abexinostat induces Cancer stem cells differentiation in breast Cancer with low Xist expression. Clin. Cancer Res. 2013, 19, 6520–6531.
98. Asghari, V.; Wang, J.F.; Reiach, J.S.; Young, L.T. Differential effects of mood stabilizers on FosrJun proteins and AP-1 DNA binding activity in human neuroblastoma SH-SY5Y cells. Mol. Brain Res. 1998, 58, 95–102.
99. Bassa, B.V.; Roh, D.D.; Vaziri, N.D.; Kirschenbaum, M.A.; Kamanna, V.S. Lysophosphatidylcholine activates mesangial cell PKC and MAP kinase by PLCgamma-1 and tyrosine kinase-Ras pathways. Am. J. Physiol. 1999, 277, F328–F337.
100. Cieslik, K.; Abrams, C.S.; Wu, K.K. Up-regulation of endothelial nitric-oxide synthase promoter by the phosphatidylinositol 3-kinase γ/Janus kinase 2/MEK-1-dependent pathway. J. Biol. Chem. 2001, 276, 1211–1219.
101. Mani, S.; Shen, Y.; Schaefer, J.; Meiri, K.F. Failure to express GAP-43 during neurogenesis affects cell cycle regulation and differentiation of neural precursors and stimulates apoptosis of neurons. Mol. Cell. Neurosci. 2001, 17, 54–66.
102. Blaheta, R.A.; Cinatl, J. Anti-tumor mechanisms of valproate: A novel role for an old drug. Med. Res. Rev. 2002, 22, 492–511.
103. Logan, C.Y.; Nusse, R. The Wnt signaling pathway in development and disease. Annu. Rev. Cell Dev. Biol 2004, 20, 781–810.
104. Bug, G.; Gul, H.; Schwarz, K.; Pfeifer, H.; Kampfmann, M.; Zheng, X.; Beissert, T.; Boehrer, S.; Hoelzer, D.; Ottmann, O.G.; Ruthardt, M. Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells. Cancer Res 2005, 65, 2537–2541.
105. Krämer, O.H.; Zhu, P.; Ostendorff, H.P.; Golebiewski, M.; Tiefenbach, J.; Peters, M.A.; Brill, B.; Groner, B.; Bach, I.; Heinzel, T., et al. The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. EMBO J. 2003, 22, 3411–3420.
106. Zupkovitz, G.; Tischler, J.; Posch, M.; Sadzak, I.; Ramsauer, K.; Egger, G.; Grausenburger, R.; Schweifer, N.; Chiocca, S.; Decker, T., et al. Negative and positive regulation of gene expression by mouse histone deacetylase 1. Mol. Cell Biol. 2006, 26, 7913–7928.
107. Montgomery, R.L.; Davis, C.A.; Potthoff, M.J.; Haberland, M.; Fielitz, J.; Qi, X.; Hill, J.A.; Richardson, J.A.; Olson, E.N. Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev. 2007, 21, 1790–1802.
108. Montgomery, R.L.; Potthoff, M.J.; Haberland, M.; Qi, X.; Matsuzaki, S.; Humphries, K.M.; Richardson, J.A.; Bassel-Duby, R.; Olson, E.N. Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice. J. Clin. Investig. 2008, 118, 3588–3597.
109. Dimmeler, S.; Fleming, I.; Fisslthaler, B.; Hermann, C.; Busse, R.; Zeiher, A.M. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 1999, 399, 601–605.
110. Fulton, D.; Gratton, J.; McCabe, T.; Fontana, J.; Fujio, Y.; Walsh, K.; Franke, T.; Papapetropoulos, A.; Sessa, W. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 1999, 399, 597–601.
111. Kawasaki, K.; Smith, R.S.; Hsieh, C.-M.; Sun, J.; Chao, J.; Liao, J.K. Activation of the phosphatidylinositol 3-kinase/protein kinase Akt pathway mediates nitric oxide-induced endothelial cell migration and angiogenesis. Mol. Cell. Biol. 2003, 23, 5726–5737.
112. Rössig, L.; Li, H.; Fisslthaler, B.; Urbich, C.; Fleming, I.; Förstermann, U.; Zeiher, A.M.; Dimmeler, S. Inhibitors of histone deacetylation downregulate the expression of endothelial nitric oxide synthase and compromise endothelial cell function in vasorelaxation and angiogenesis. Circ. Res. 2002, 91, 837–844.
113. Deroanne, C.F.; Bonjean, K.; Servotte, S.; Devy, L.; Colige, A.; Clausse, N.; Blacher, S.; Verdin, E.; Foidart, J.-M.; Nusgens, B.V., et al. Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene 2002, 21, 427–436.
114. Cinatl, J.; Kotchetkov, R.; Blaheta, R.; Driever, P.H.; Vogel, J.U.; Cinatl, J. Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)-C cells by valproic acid: Enhancement by combination with interferon-α. Int. J. Oncol. 2002, 20, 97–106.
115. Chelluri, R.; Caza, T.; Woodford, M.R.; Reeder, J.E.; Bratslavsky, G.; Byler, T. Valproic acid alters angiogenic and trophic gene expression in human prostate cancer models. Anticancer Res. 2016, 36, 5079–5086.
116. Michaelis, M.; Suhan, T.; Michaelis, U.R.; Beek, K.; Rothweiler, F.; Tausch, L.; Werz, O.; Eikel, D.; Zörnig, M.; Nau, H., et al. Valproic acid induces extracellular signal-regulated kinase 1/2 activation and inhibits apoptosis in endothelial cells. Cell Death Differ. 2006, 13, 446–453.
117. Lin, K.T.; Wang, Y.W.; Chen, C.T.; Ho, C.M.; Su, W.H.; Jou, Y.S. HDAC inhibitors augmented cell migration and metastasis through induction of PKCs leading to identification of low toxicity modalities for combination cancer therapy. Clin. Cancer Res. 2012, 18, 4691–4701.
118. Setiadi, A.F.; Omilusik, K.; David, M.D.; Seipp, R.P.; Hartikainen, J.; Gopaul, R.; Choi, K.B.; Jefferies, W.A. Epigenetic enhancement of antigen processing and presentation promotes immune recognition of tumors. Cancer Res. 2008, 68, 9601–9607.
119. Balliu, M.; Guandalini, L.; Romanelli, M.N.; D’Amico, M.; Paoletti, F. HDAC-inhibitor (S)-8 disrupts HDAC6-PP1 complex prompting A375 melanoma cell growth arrest and apoptosis. J. Cell. Mol. Med. 2015, 19, 143–154.
120. Woan, K.V.; Lienlaf, M.; Perez-Villaroel, P.; Lee, C.; Cheng, F.; Knox, T.; Woods, D.M.; Barrios, K.; Powers, J.; Sahakian, E., et al. Targeting histone deacetylase 6 mediates a dual anti-melanoma effect: Enhanced antitumor immunity and impaired cell proliferation. Mol. Oncol. 2015, 9, 1447–1457.
121. Cheng, F.; Lienlaf, M.; Wang, H.-W.; Perez-Villarroel, P.; Lee, C.; Woan, K.; Rock-Klotz, J.; Sahakian, E.; Woods, D.; Pinilla-Ibarz, J., et al. A novel role for histone deacetylase 6 in the regulation of the tolerogenic STAT3/IL-10 pathway in APCs. J. Immunol. 2014, 193, 2850–2862.
122. Kroesen, M.; Gielen, P.; Brok, I.C.; Armandari, I.; Hoogerbrugge, P.M.; Adema, G.J. HDAC inhibitors and immunotherapy; a double edged sword? Oncotarget 2014, 5, 6558–6572.
123. Gameiro, S.R.; Malamas, A.S.; Tsang, K.Y.; Ferrone, S.; Hodge, J.W. Inhibitors of histone deacetylase 1 reverse the immune evasion phenotype to enhance T-cell mediated lysis of prostate and breast carcinoma cells. Oncotarget 2016, 7, 7390–7402.
124. Sabbatino, F.; Schwab, J.H.; Ferrone, S.; Ferrone, C.R. Evolution of studies of HLA class I antigen processing machinery (APM) components in malignant cells. Clin. Transpl. 2013, 1, 453–463.
125. Rooney, M.S.; Shukla, S.A.; Wu, C.J.; Getz, G.; Hacohen, N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 2015, 160, 48–61.
126. Kortenhorst, M.S.; Wissing, M.D.; Rodríguez, R.; Kachhap, S.K.; Jans, J.J.; Van der Groep, P.; Verheul, H.M.; Gupta, A.; Aiyetan, P.O.; van der Wall, E., et al. Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors. Epigenetics 2013, 8, 907–920.
127. Higuchi, A.; Ling, Q.-D.; Kumar, S.S.; Munusamy, M.A.; Alarfaj, A.A.; Chang, Y.; Kao, S.-H.; Lin, K.-C.; Wang, H.-C.; Umezawa, A. Generation of pluripotent stem cells without the use of genetic material. Lab. Investig. 2015, 95, 26–42.
128. Burba, I.; Colombo, G.I.; Staszewsky, L.I.; De Simone, M.; Devanna, P.; Nanni, S.; Avitabile, D.; Molla, F.; Cosentino, S.; Russo, I., et al. Histone deacetylase inhibition enhances self renewal and cardioprotection by human cord blood-derived CD34 cells. PLoS ONE 2011, 6, e22158.
129. Feng, J.; Cen, J.; Li, J.; Zhao, R.; Zhu, C.; Wang, Z.; Xie, J.; Tang, W. Histone deacetylase inhibitor valproic acid (VPA) promotes the epithelial mesenchymal transition of colorectal cancer cells via up regulation of Snail. Cell Adhes. Migr. 2015, 9, 495–501.
130. Wu, S.; Luo, Z.; Yu, P.-J.; Xie, H.; He, Y.-W. Suberoylanilide hydroxamic acid (SAHA) promotes the epithelial mesenchymal transition of triple negative breast cancer cells via HDAC8/FOXA1 signals. Biol. Chem. 2016, 397, 75–83.
131. Tabu, K.; Sasai, K.; Kimura, T.; Wang, L.; Aoyanagi, E.; Kohsaka, S.; Tanino, M.; Nishihara, H.; Tanaka, S. Promoter hypomethylation regulates CD133 expression in human gliomas. Cell Res. 2008, 18, 1037–1046.
132. Zhu, J.; Wan, H.; Xue, C.; Jiang, T.; Qian, C.; Zhang, Y. Histone deacetylase 3 implicated in the pathogenesis of children glioma by promoting glioma cell proliferation and migration. Brain Res. 2013, 1520, 15–22.
133. Khalil, M.A.; Hraběta, J.; Groh, T.; Procházka, P.; Doktorová, H.; Eckschlager, T. Valproic acid increases CD133 positive cells that show low sensitivity to cytostatics in neuroblastoma. PLoS ONE 2016, 11, e0162916.
134. Rudà, R.; Pellerino, A.; Soffietti, R. Does valproic acid affect tumor growth and improve survival in glioblastomas? CNS Oncol. 2016, 5, 51–53.
135. Hřebačková, J.; Poljaková, J.; Eckschlager, T.; Hraběta, J.; Procházka, P.; Smutný, S.; Stiborová, M. Histone deacetylase inhibitors valproate and trichostatin A are toxic to neuroblastoma cells and modulate cytochrome P450 1A1, 1B1 and 3A4 expression in these cells. Interdiscip. Toxicol. 2009, 2, 205–210.
136. Bose, P.; Dai, Y.; Grant, S. Histone deacetylase inhibitor (HDACI) mechanisms of action: Emerging insights. Pharmacol. Ther. 2014, 143, 323–336.
137. Bhaskara, S. Histone deacetylases 1 and 2 regulate DNA replication and DNA repair: Potential targets for genome stability-mechanism-based therapeutics for a subset of cancers. Cell Cycle 2015, 14, 1779–1785.
138. Dowdy, S.C.; Jiang, S.; Zhou, X.C.; Hou, X.; Jin, F.; Podratz, K.C.; Jiang, S.-W. Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells. Mol. Cancer Ther. 2006, 5, 2767–2776.
139. Engel, J.A.; Jones, A.J.; Avery, V.M.; Sumanadasa, S.D.M.; Ng, S.S.; Fairlie, D.P.; Adams, T.S.; Andrews, K.T. Profiling the anti-protozoal activity of anti-cancer HDAC inhibitors against Plasmodium and Trypanosoma parasites. Int. J. Parasitol. Drugs Drug Resist. 2015, 5, 117–126.
140. Namdar, M.; Perez, G.; Ngo, L.; Marks, P.A. Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents. Proc. Natl. Acad. Sci. USA 2010, 107, 20003–20008.
141. Ma, X.; Ezzeldin, H.H.; Diasio, R.B. Histone deacetylase inhibitors: Current status and overview of recent clinical trials. Drugs 2009, 69, 1911–1934.
142. Chen, M.Y.; Liao, W.S.L.; Lu, Z.; Bornmann, W.G.; Hennessey, V.; Washington, M.N.; Rosner, G.L.; Yu, Y.; Ahmed, A.A.; Bast, R.C. Decitabine and suberoylanilide hydroxamic acid (SAHA) inhibit growth of ovarian cancer cell lines and xenografts while inducing expression of imprinted tumor suppressor genes, apoptosis, G2/M arrest, and autophagy. Cancer 2011, 117, 4424–4438.
143. Yang, H.; Hoshino, K.; Sanchez-Gonzalez, B.; Kantarjian, H.; Garcia-Manero, G. Antileukemia activity of the combination of 5-aza-2′-deoxycytidine with valproic acid. Leuk. Res. 2005, 29, 739–748.
144. Ecke, I.; Petry, F.; Rosenberger, A.; Tauber, S.; Mo, S.; Hess, I.; Dullin, C.; Kimmina, S.; Pirngruber, J.; Johnsen, S.A., et al. Antitumor Effects of a Combined 5-Aza-2′ Deoxycytidine and Valproic Acid Treatment on Rhabdomyosarcoma and Medulloblastoma in Ptch Mutant Mice. Cancer Res. 2009, 69, 887–896.
145. Klisovic, M.I.; Maghraby, E.A.; Parthun, M.R.; Guimond, M.; Sklenar, A.R.; Whitman, S.P.; Chan, K.K.; Murphy, T.; Anon, J.; Archer, K.J., et al. Depsipeptide (FR 901228) promotes histone acetylation, gene transcription, apoptosis and its activity is enhanced by DNA methyltransferase inhibitors in AML1/ETO-positive leukemic cells. Leukemia 2003, 17, 350–358.
146. Chai, G.; Li, L.; Zhou, W.; Wu, L.; Zhao, Y.; Wang, D.; Lu, S.; Yu, Y.; Wang, H.; McNutt, M.A., et al. HDAC inhibitors act with 5-aza-2′-deoxycytidine to inhibit cell proliferation by suppressing removal of incorporated abases in lung cancer cells. PLoS ONE 2008, 3, e2445.
147. Hu, Y.; Lu, W.; Chen, G.; Zhang, H.; Jia, Y.; Wei, Y.; Yang, H.; Zhang, W.; Fiskus, W.; Bhalla, K., et al. Overcoming resistance to histone deacetylase inhibitors in human leukemia with the redox modulating compound β-phenylethyl isothiocyanate. Blood 2010, 116, 2732–2741.
148. Greve, G.; Schiffmann, I.; Pfeifer, D.; Pantic, M.; Schüler, J.; Lübbert, M. The pan-HDAC inhibitor panobinostat acts as a sensitizer for erlotinib activity in EGFR-mutated and -wildtype non-small cell lung cancer cells. BMC Cancer 2015, 15, 947–957.
149. Takashina, T.; Kinoshita, I.; Kikuchi, J.; Shimizu, Y.; Sakakibara-Konishi, J.; Oizumi, S.; Nishimura, M.; Dosaka-Akita, H. Combined inhibition of EZH2 and histone deacetylases as a potential epigenetic therapy for non-small-cell lung cancer cells. Cancer Sci. 2016, 107, 955–962.
150. Pei, X.-Y.; Dai, Y.; Grant, S. Synergistic Induction of Oxidative Injury and Apoptosis in Human Multiple Myeloma Cells by the Proteasome Inhibitor Bortezomib and Histone Deacetylase Inhibitors. Clin. Cancer Res. 2004, 10, 3839–3852.
151. Nawrocki, S.T.; Carew, J.S.; Pino, M.S.; Highshaw, R.A.; Andtbacka, R.H.I.; Dunner, K.; Pal, A.; Bornmann, W.G.; Chiao, P.J.; Huang, P., et al. Aggresome disruption: A novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells. Cancer Res. 2006, 66, 3773–3781.
152. Dasmahapatra, G.; Lembersky, D.; Kramer, L.; Fisher, R.I.; Friedberg, J.; Dent, P.; Grant, S. The pan-HDAC inhibitor vorinostat potentiates the activity of the proteasome inhibitor carfilzomib in human DLBCL cells in vitro and in vivo. Blood 2010, 115, 4478–4487.
153. Dasmahapatra, G.; Lembersky, D.; Son, M.P.; Attkisson, E.; Dent, P.; Fisher, R.I.; Friedberg, J.W.; Grant, S. Carfilzomib interacts synergistically with histone deacetylase inhibitors in mantle cell lymphoma cells in vitro and in vivo. Mol. Cancer Ther. 2011, 10, 1686–1697.
154. Groh, T.; Hrabeta, J.; Khalil, M.A.; Doktorova, H.; Eckschlager, T.; Stiborova, M. The synergistic effects of DNA-damaging drugs cisplatin and etoposide with a histone deacetylase inhibitor valproate in high-risk neuroblastoma cells. Int. J. Oncol. 2015, 47, 343–352.
155. Luchenko, V.L.; Salcido, C.D.; Zhang, Y.; Agama, K.; Komlodi-Pasztor, E.; Murphy, R.F.; Giaccone, G.; Pommier, Y.; Bates, S.E.; Varticovski, L. Schedule-dependent synergy of histone deacetylase inhibitors with DNA damaging agents in small cell lung cancer. Cell Cycle 2011, 10, 3119–3128.
156. Kim, M.S.; Blake, M.; Baek, J.H.; Kohlhagen, G.; Pommier, Y.; Carrier, F. Inhibition of Histone Deacetylase Increases Cytotoxicity to Anticancer Drugs Targeting DNA. Cancer Res. 2003, 63, 7291–7300.
157. Catalano, M.G.; Poli, R.; Pugliese, M.; Fortunati, N.; Boccuzzi, G. Valproic acid enhances tubulin acetylation and apoptotic activity of paclitaxel on anaplastic thyroid cancer cell lines. Endocr. Relat. Cancer 2007, 14, 839–845.
158. Ryu, C.H.; Yoon, W.S.; Park, K.Y.; Kim, S.M.; Lim, J.Y.; Woo, J.S.; Jeong, C.H.; Hou, Y.; Jeun, S.S. Valproic acid downregulates the expression of MGMT and sensitizes temozolomide-resistant glioma cells. J. Biomed. Biotechnol. 2012, 2012, 987495.
159. Griffiths, E.A.; Gore, S.D. DNA Methyltransferase and Histone Deacetylase Inhibitors in the Treatment of Myelodysplastic Syndromes. Semin. Hematol. 2008, 45, 23–30.
160. Rudek, M.A.; Zhao, M.; He, P.; Hartke, C.; Gilbert, J.; Gore, S.D.; Carducci, M.A.; Baker, S.D. Pharmacokinetics of 5-azacitidine administered with phenylbutyrate in patients with refractory solid tumors or hematologic malignancies. J. Clin. Oncol. 2005, 23, 3906–3911.
161. Badros, A.; Burger, A.M.; Philip, S.; Niesvizky, R.; Kolla, S.S.; Goloubeva, O.; Harris, C.; Zwiebel, J.; Wright, J.J.; Espinoza-Delgado, I., et al. Phase I study of vorinostat in combination with bortezomib for relapsed and refractory multiple myeloma. Clin. Cancer Res. 2009, 15, 5250–5257.
162. Mazumder, A.; Vesole, D.H.; Jagannath, S. Vorinostat plus bortezomib for the treatment of relapsed/refractory multiple myeloma: A case series illustrating utility in clinical practice. Clin. Lymphoma Myeloma Leuk. 2010, 10, 149–151.
163. Afifi, S.; Michael, A.; Azimi, M.; Rodriguez, M.; Lendvai, N.; Landgren, O. Role of Histone Deacetylase Inhibitors in Relapsed Refractory Multiple Myeloma: A Focus on Vorinostat and Panobinostat. Pharmacotherapy 2015, 35, 1173–1188.
164. Garcia-Manero, G.; Tambaro, F.P.; Bekele, N.B.; Yang, H.; Ravandi, F.; Jabbour, E.; Borthakur, G.; Kadia, T.M.; Konopleva, M.Y.; Faderl, S., et al. Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome. J. Clin. Oncol. 2012, 30, 2204–2210.
165. Khan, I.; Altman, J.K.; Licht, J.D. New strategies in acute myeloid leukemia: Redefining prognostic markers to guide therapy. Clin. Cancer Res. 2012, 18, 5163–5171.
166. Duvic, M.; Talpur, R.; Ni, X.; Zhang, C.; Hazarika, P.; Kelly, C.; Chiao, J.H.; Reilly, J.F.; Ricker, J.L.; Richon, V.M., et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 2007, 109, 31–39.
167. Olsen, E.A.; Kim, Y.H.; Kuzel, T.M.; Pacheco, T.R.; Foss, F.M.; Parker, S.; Frankel, S.R.; Chen, C.; Ricker, J.L.; Arduino, J.M., et al. Phase IIB Multicenter Trial of Vorinostat in Patients With Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma. J. Clin. Oncol. 2007, 25, 3109–3115.
168. Blum, W.; Marcucci, G. Targeting epigenetic changes in acute myeloid leukemia. Clin. Adv. Hematol. Oncol. 2005, 3, 855–865.
169. Garcia-Manero, G.; Yang, H.; Bueso-Ramos, C.; Ferrajoli, A.; Cortes, J.; Wierda, W.G.; Faderl, S.; Koller, C.; Morris, G.; Rosner, G., et al. Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes. Blood 2008, 111, 1060–1066.
170. Ghobrial, I.M.; Campigotto, F.; Murphy, T.J.; Boswell, E.N.; Banwait, R.; Azab, F.; Chuma, S.; Kunsman, J.; Donovan, A.; Masood, F., et al. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia. Blood 2013, 121, 1296–1303.
171. Blum, K.A.; Advani, A.; Fernandez, L.; Van Der Jagt, R.; Brandwein, J.; Kambhampati, S.; Kassis, J.; Davis, M.; Bonfils, C.; Dubay, M., et al. Phase II study of the histone deacetylase inhibitor MGCD0103 in patients with previously treated chronic lymphocytic leukaemia. Br. J. Haematol. 2009, 147, 507–514.
172. Ellis, L.; Bots, M.; Lindemann, R.K.; Bolden, J.E.; Newbold, A.; Cluse, L.A.; Scott, C.L.; Strasser, A.; Atadja, P.; Lowe, S.W., et al. The histone deacetylase inhibitors LAQ824 and LBH589 do not require death receptor signaling or a functional apoptosome to mediate tumor cell death or therapeutic efficacy. Blood 2009, 114, 380–393.
173. Giles, F.; Fischer, T.; Cortes, J.; Garcia-Manero, G.; Beck, J.; Ravandi, F.; Masson, E.; Rae, P.; Laird, G.; Sharma, S., et al. A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies. Clin. Cancer Res. 2006, 12, 4628–4635.
174. Gryder, B.E.; Sodji, Q.H.; Oyelere Adegboyega K Targeted cancer therapy: Giving histone deacetylase inhibitors all they need to succeed. Futur. Med Chem. 2012, 4, 505–524.
175. O’connor, O.A.; Heaney, M.L.; Schwartz, L.; Richardson, S.; Willim, R.; MacGregor-Cortelli, B.; Curly, T.; Moskowitz, C.; Portlock, C.; Horwitz, S. Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic acid in patients with advanced hematologic malignancies. J. Clin. Oncol. 2006, 24, 166–173.
176. Weller, M.; Gorlia, T.; Cairncross, J.G.; Van Den Bent, M.J.; Mason, W.; Belanger, K.; Brandes, A.A.; Bogdahn, U.; Macdonald, D.R.; Forsyth, P., et al. Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma. Neurology 2011, 77, 1156–1164.
177. Scherpereel, A.; Berghmans, T.; Lafitte, J.J.; Colinet, B.; Richez, M.; Bonduelle, Y.; Meert, A.P.; Dhalluin, X.; Leclercq, N.; Paesmans, M., et al. Valproate-doxorubicin: Promising therapy for progressing mesothelioma. A phase II study. Eur. Respir. J. 2011, 37, 129–135.
178. Ramalingam, S.S.; Maitland, M.L.; Frankel, P.; Argiris, A.E.; Koczywas, M.; Gitlitz, B.; Thomas, S.; Espinoza-Delgado, I.; Vokes, E.E.; Gandara, D.R., et al. Carboplatin and Paclitaxel in combination with either vorinostat or placebo for first-line therapy of advanced non-small-cell lung cancer. J. Clin. Oncol. 2010, 28, 56–62.
179. Munster, P.N.; Thurn, K.T.; Thomas, S.; Raha, P.; Lacevic, M.; Miller, A.; Melisko, M.; Ismail-Khan, R.; Rugo, H.; Moasser, M., et al. A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer. Br. J. Cancer 2011, 104, 1828–1835.
180. Witta, S.E.; Jotte, R.M.; Konduri, K.; Neubauer, M.A.; Spira, A.I.; Ruxer, R.L.; Varella-Garcia, M.; Bunn, P.A.; Hirsch, F.R. Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy. J. Clin. Oncol. 2012, 30, 2248–2255.
181. Ahuja, N.; Sharma, A.R.; Baylin, S.B. Epigenetic therapeutics: A new weapon in the war against cancer. Annu. Rev. Med. 2016, 67, 73–89.