Advanced Biomedical Research

Histone Deacetylases and Histone Deacetylase Inhibitors: Molecular Mechanisms of Action in Various Cancers

Reviewers

Authors

Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran

Abstract

Epigenetic modifications such as histone modification play an important role in tumorigenesis. There are several evidence that histone deacetylases (HDACs) play a key role in cancer induction and progression by histone deacetylation. Besides, histone acetylation is being accessed as a therapeutic target because of its role in regulating gene expression. HDAC inhibitors (HDACIs) are a family of synthetic and natural compounds that differ in their target specificities and activities. They affect markedly cancer cells, inducing cell differentiation, cell cycle arrest and cell death, reduction of angiogenesis, and modulation of the immune system. Here, we summarize the mechanisms of HDACs and the HDACIs in several cancers. An online search of different sources such as PubMed, ISI, and Scopus was performed to find available data on mechanisms and pathways of HDACs and HDACIs in different cancers. The result indicated that HDACs induce cancer through multiple mechanisms in various tissues. This effect can be inhibited by HDACIs which affect cancer cell by different pathways such as cell differentiation, cell cycle arrest, and cell death. In conclusion, these findings indicate that the HDACs play a major role in carcinogenesis through various pathways, and HDACIs can inhibit HDAC activity by multiple mechanisms resulting in cell cycle arrest, cell growth inhibition, and apoptosis induction.

Keywords

1.
Yoshida M, Kudo N, Kosono S, Ito A. Chemical and structural biology of protein lysine deacetylases. Proc Jpn Acad Ser B Phys Biol Sci 2017;93:297-321.  Back to cited text no. 1
    
2.
Khochbin S, Verdel A, Lemercier C, Seigneurin-Berny D. Functional significance of histone deacetylase diversity. Curr Opin Genet Dev 2001;11:162-6.  Back to cited text no. 2
    
3.
Jones JD, O'Connor CD. Protein acetylation in prokaryotes. Proteomics 2011;11:3012-22.  Back to cited text no. 3
    
4.
Allis CD, Berger SL, Cote J, Dent S, Jenuwien T, Kouzarides T, et al. New nomenclature for chromatin-modifying enzymes. Cell 2007;131:633-6.  Back to cited text no. 4
    
5.
Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006;5:769-84.  Back to cited text no. 5
    
6.
Hrabeta J, Stiborova M, Adam V, Kizek R, Eckschlager T. Histone deacetylase inhibitors in cancer therapy. A review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158:161-9.  Back to cited text no. 6
    
7.
Hull EE, Montgomery MR, Leyva KJ. HDAC inhibitors as epigenetic regulators of the immune system: Impacts on cancer therapy and inflammatory diseases. Biomed Res Int 2016; 10: 1-15.  Back to cited text no. 7
    
8.
Ceccacci E, Minucci S. Inhibition of histone deacetylases in cancer therapy: Lessons from leukaemia. Br J Cancer 2016; 114:605-11.  Back to cited text no. 8
    
9.
Kavoosi F, Sanaei M. Comparative analysis of the effects of valproic acid and tamoxifen on proliferation, and apoptosis of human hepatocellular carcinoma WCH 17 celllin. Iran J Peadiatr Hematol Oncol 2018;8:12-20.  Back to cited text no. 9
    
10.
Sanaei M, Kavoosi F, Atashpour S, Haghighat S. Effects of genistein and synergistic action in combination with tamoxifen on the hepG2 human hepatocellular carcinoma cell line Asian Pac J Cancer Prev 2017;18:2381-5.  Back to cited text no. 10
    
11.
Sanaei M, Kavoosi F, Pourahmadi M, Moosavi SN. Effect of genistein and 17-β estradiol on the viability and apoptosis of human hepatocellular carcinoma hepG2 cell line. Adv Biomed Res 2017;6:163.  Back to cited text no. 11
[PUBMED]  [Full text]  
12.
Singh AK, Bishayee A, Pandey AK. Targeting histone deacetylases with natural and synthetic agents: An emerging anticancer strategy. Nutrients 2018;10. pii: E731.  Back to cited text no. 12
    
13.
Shahbazian MD, Grunstein M. Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 2007;76:75-100.  Back to cited text no. 13
    
14.
Dawson MA, Kouzarides T. Cancer epigenetics: From mechanism to therapy. Cell 2012;150:12-27.  Back to cited text no. 14
    
15.
Cress WD, Seto E. Histone deacetylases, transcriptional control, and cancer. J Cell Physiol 2000;184:1-6.  Back to cited text no. 15
    
16.
Senese S, Zaragoza K, Minardi S, Muradore I, Ronzoni S, Passafaro A, et al. Role for histone deacetylase 1 in human tumor cell proliferation. Mol Cell Biol 2007;27:4784-95.  Back to cited text no. 16
    
17.
Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J, et al. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One 2008;3:e2020.  Back to cited text no. 17
    
18.
Verdin E, Dequiedt F, Kasler HG. Class II histone deacetylases: Versatile regulators. Trends Genet 2003;19:286-93.  Back to cited text no. 18
    
19.
Kim HJ, Bae SC. Histone deacetylase inhibitors: Molecular mechanisms of action and clinical trials as anti-cancer drugs. Am J Transl Res 2011;3:166-79.  Back to cited text no. 19
    
20.
Yang Q, Yang Y, Zhou N, Tang K, Lau WB, Lau B, et al. Epigenetics in ovarian cancer: Premise, properties, and perspectives. Mol Cancer 2018;17:109.  Back to cited text no. 20
    
21.
Hodawadekar SC, Marmorstein R. Chemistry of acetyl transfer by histone modifying enzymes: Structure, mechanism and implications for effector design. Oncogene 2007;26:5528-40.  Back to cited text no. 21
    
22.
Parthun MR. Hat1: The emerging cellular roles of a type B histone acetyltransferase. Oncogene 2007;26:5319-28.  Back to cited text no. 22
    
23.
Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res 2011;21:381-95.  Back to cited text no. 23
    
24.
Siu LL, Pili R, Duran I, Messersmith WA, Chen EX, Sullivan R, et al. Phase I study of MGCD0103 given as a three-times-per-week oral dose in patients with advanced solid tumors. J Clin Oncol 2008;26:1940-7.  Back to cited text no. 24
    
25.
Zhang Z, Hao C, Wang L, Liu P, Zhao L, Zhu C, et al. Inhibition of leukemic cells by valproic acid, an HDAC inhibitor, in xenograft tumors. Onco Targets Ther 2013;6:733-40.  Back to cited text no. 25
    
26.
Mottamal M, Zheng S, Huang TL, Wang G. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules 2015;20:3898-941.  Back to cited text no. 26
    
27.
Fritzsche FR, Weichert W, Röske A, Gekeler V, Beckers T, Stephan C, et al. Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer. BMC Cancer 2008;8:381.  Back to cited text no. 27
    
28.
Kato Y, Yoshimura K, Shin T, Verheul H, Hammers H, Sanni TB, et al. Synergisticin vivo antitumor effect of the histone deacetylase inhibitor MS-275 in combination with interleukin 2 in a murine model of renal cell carcinoma. Clin Cancer Res 2007;13:4538-46.  Back to cited text no. 28
    
29.
Wang XF, Qian DZ, Ren M, Kato Y, Wei Y, Zhang L, et al. Epigenetic modulation of retinoic acid receptor beta2 by the histone deacetylase inhibitor MS-275 in human renal cell carcinoma. Clin Cancer Res 2005;11:3535-42.  Back to cited text no. 29
    
30.
Cha TL, Chuang MJ, Wu ST, Sun GH, Chang SY, Yu DS, et al. Dual degradation of aurora A and B kinases by the histone deacetylase inhibitor LBH589 induces G2-M arrest and apoptosis of renal cancer cells. Clin Cancer Res 2009;15:840-50.  Back to cited text no. 30
    
31.
Poyet C, Jentsch B, Hermanns T, Schweckendiek D, Seifert HH, Schmidtpeter M, et al. Expression of histone deacetylases 1, 2 and 3 in urothelial bladder cancer. BMC Clin Pathol 2014;14:10.  Back to cited text no. 31
    
32.
Wild PJ, Herr A, Wissmann C, Stoehr R, Rosenthal A, Zaak D, et al. Gene expression profiling of progressive papillary noninvasive carcinomas of the urinary bladder. Clin Cancer Res 2005;11:4415-29.  Back to cited text no. 32
    
33.
Ozawa A, Tanji N, Kikugawa T, Sasaki T, Yanagihara Y, Miura N, et al. Inhibition of bladder tumour growth by histone deacetylase inhibitor. BJU Int 2010;105:1181-6.  Back to cited text no. 33
    
34.
Gui CY, Ngo L, Xu WS, Richon VM, Marks PA. Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. Proc Natl Acad Sci U S A 2004;101:1241-6.  Back to cited text no. 34
    
35.
Chopin V, Toillon RA, Jouy N, Le Bourhis X. P21(WAF1/CIP1) is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cells. Oncogene 2004;23:21-9.  Back to cited text no. 35
    
36.
Jones J, Juengel E, Mickuckyte A, Hudak L, Wedel S, Jonas D, et al. The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinomain vitro and in vivo. J Cell Mol Med 2009;13:2376-85.  Back to cited text no. 36
    
37.
Sami S, Höti N, Xu HM, Shen Z, Huang X. Valproic acid inhibits the growth of cervical cancer bothin vitro and in vivo. J Biochem 2008;144:357-62.  Back to cited text no. 37
    
38.
Lagger G, O'Carroll D, Rembold M, Khier H, Tischler J, Weitzer G, et al. Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. EMBO J 2002;21:2672-81.  Back to cited text no. 38
    
39.
Nakagawa M, Oda Y, Eguchi T, Aishima S, Yao T, Hosoi F, et al. Expression profile of class I histone deacetylases in human cancer tissues. Oncol Rep 2007;18:769-74.  Back to cited text no. 39
    
40.
Waltregny D, North B, Van Mellaert F, de Leval J, Verdin E, Castronovo V. Screening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class I HDAC profiles between epithelial and stromal cells. Eur J Histochem 2004;48:273-90.  Back to cited text no. 40
    
41.
Weichert W, Röske A, Gekeler V, Beckers T, Stephan C, Jung K, et al. Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy. Br J Cancer 2008;98:604-10.  Back to cited text no. 41
    
42.
Chen CS, Wang YC, Yang HC, Huang PH, Kulp SK, Yang CC, et al. Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting ku70 acetylation. Cancer Res 2007;67:5318-27.  Back to cited text no. 42
    
43.
Jung M, Kozikowski A, Dritschilo A. Rational design and development of radiation-sensitizing histone deacetylase inhibitors. Chem Biodivers 2005;2:1452-61.  Back to cited text no. 43
    
44.
Abbas A, Gupta S. The role of histone deacetylases in prostate cancer. Epigenetics 2008;3:300-9.  Back to cited text no. 44
    
45.
Khabele D, Son DS, Parl AK, Goldberg GL, Augenlicht LH, Mariadason JM, et al. Drug-induced inactivation or gene silencing of class I histone deacetylases suppresses ovarian cancer cell growth: Implications for therapy. Cancer Biol Ther 2007;6:795-801.  Back to cited text no. 45
    
46.
Weichert W, Denkert C, Noske A, Darb-Esfahani S, Dietel M, Kalloger SE, et al. Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinomas. Neoplasia 2008;10:1021-7.  Back to cited text no. 46
    
47.
Cacan E. Epigenetic regulation of RGS2 (Regulator of G-protein signaling 2) in chemoresistant ovarian cancer cells. J Chemother 2017;29:173-8.  Back to cited text no. 47
    
48.
Hayashi A, Horiuchi A, Kikuchi N, Hayashi T, Fuseya C, Suzuki A, et al. 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;127:1332-46.  Back to cited text no. 48
    
49.
Takai N, Narahara H. Histone deacetylase inhibitor therapy in epithelial ovarian cancer. J Oncol 2010; 5: 1-6.  Back to cited text no. 49
    
50.
Weberpals JI, O'Brien AM, Niknejad N, Garbuio KD, Clark-Knowles KV, Dimitroulakos J. The effect of the histone deacetylase inhibitor M344 on BRCA1 expression in breast and ovarian cancer cells. Cancer Cell Int 2011;11:29.  Back to cited text no. 50
    
51.
Muscolini M, Cianfrocca R, Sajeva A, Mozzetti S, Ferrandina G, Costanzo A, et al. Trichostatin A up-regulates p73 and induces bax-dependent apoptosis in cisplatin-resistant ovarian cancer cells. Mol Cancer Ther 2008;7:1410-9.  Back to cited text no. 51
    
52.
Takai N, Kawamata N, Gui D, Said JW, Miyakawa I, Koeffler HP. Human ovarian carcinoma cells: Histone deacetylase inhibitors exhibit antiproliferative activity and potently induce apoptosis. Cancer 2004;101:2760-70.  Back to cited text no. 52
    
53.
Takai N, Narahara H. Human endometrial and ovarian cancer cells: Histone deacetylase inhibitors exhibit antiproliferative activity, potently induce cell cycle arrest, and stimulate apoptosis. Curr Med Chem 2007;14:2548-53.  Back to cited text no. 53
    
54.
Cuppens T, Tuyaerts S, Amant F. Potential therapeutic targets in uterine sarcomas. Sarcoma 2015; 3: 1-14.  Back to cited text no. 54
    
55.
Marchion D, Münster P. Development of histone deacetylase inhibitors for cancer treatment. Expert Rev Anticancer Ther 2007;7:583-98.  Back to cited text no. 55
    
56.
Takai N, Narahara H. Preclinical studies of chemotherapy using histone deacetylase inhibitors in endometrial cancer. Obstet Gynecol Int 2010; 6: 1-8.  Back to cited text no. 56
    
57.
Vanaja GR, Ramulu HG, Kalle AM. Overexpressed HDAC8 in cervical cancer cells shows functional redundancy of tubulin deacetylation with HDAC6. Cell Commun Signal 2018;16:20.  Back to cited text no. 57
    
58.
Feng D, Wu J, Tian Y, Zhou H, Zhou Y, Hu W, et al. Targeting of histone deacetylases to reactivate tumour suppressor genes and its therapeutic potential in a human cervical cancer xenograft model. PLoS One 2013;8:e80657.  Back to cited text no. 58
    
59.
Huang BH, Laban M, Leung CH, Lee L, Lee CK, Salto-Tellez M, et al. Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1. Cell Death Differ 2005;12:395-404.  Back to cited text no. 59
    
60.
Atmaca A, Al-Batran SE, Maurer A, Neumann A, Heinzel T, Hentsch B, et al. Valproic acid (VPA) in patients with refractory advanced cancer: A dose escalating phase I clinical trial. Br J Cancer 2007;97:177-82.  Back to cited text no. 60
    
61.
Krusche CA, Wülfing P, Kersting C, Vloet A, Böcker W, Kiesel L, et al. Histone deacetylase-1 and -3 protein expression in human breast cancer: A tissue microarray analysis. Breast Cancer Res Treat 2005;90:15-23.  Back to cited text no. 61
    
62.
Zhang Z, Yamashita H, Toyama T, Sugiura H, Omoto Y, Ando Y, et al. HDAC6 expression is correlated with better survival in breast cancer. Clin Cancer Res 2004;10:6962-8.  Back to cited text no. 62
    
63.
Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 2006;6:38-51.  Back to cited text no. 63
    
64.
Dokmanovic M, Marks PA. Prospects: Histone deacetylase inhibitors. J Cell Biochem 2005;96:293-304.  Back to cited text no. 64
    
65.
Zhou Q, Atadja P, Davidson NE. Histone deacetylase inhibitor LBH589 reactivates silenced estrogen receptor alpha (ER) gene expression without loss of DNA hypermethylation. Cancer Biol Ther 2007;6:64-9.  Back to cited text no. 65
    
66.
Pruitt K, Zinn RL, Ohm JE, McGarvey KM, Kang SH, Watkins DN, et al. Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation. PLoS Genet 2006;2:e40.  Back to cited text no. 66
    
67.
Pathiraja TN, Stearns V, Oesterreich S. Epigenetic regulation in estrogen receptor positive breast cancer – Role in treatment response. J Mammary Gland Biol Neoplasia 2010;15:35-47.  Back to cited text no. 67
    
68.
Zhu P, Martin E, Mengwasser J, Schlag P, Janssen KP, Göttlicher M. Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. Cancer Cell 2004;5:455-63.  Back to cited text no. 68
    
69.
Dashwood RH, Ho E. Dietary histone deacetylase inhibitors: From cells to mice to man. Semin Cancer Biol 2007;17:363-9.  Back to cited text no. 69
    
70.
Stypula-Cyrus Y, Damania D, Kunte DP, Cruz MD, Subramanian H, Roy HK, et al. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure. PLoS One 2013;8:e64600.  Back to cited text no. 70
    
71.
Chou CW, Wu MS, Huang WC, Chen CC. HDAC inhibition decreases the expression of EGFR in colorectal cancer cells. PLoS One 2011;6:e18087.  Back to cited text no. 71
    
72.
LaBonte MJ, Wilson PM, Fazzone W, Groshen S, Lenz HJ, Ladner RD. DNA microarray profiling of genes differentially regulated by the histone deacetylase inhibitors vorinostat and LBH589 in colon cancer cell lines. BMC Med Genomics 2009;2:67.  Back to cited text no. 72
    
73.
Quint K, Agaimy A, Di Fazio P, Montalbano R, Steindorf C, Jung R, et al. Clinical significance of histone deacetylases 1, 2, 3, and 7: HDAC2 is an independent predictor of survival in HCC. Virchows Arch 2011;459:129-39.  Back to cited text no. 73
    
74.
Liu C, Liu L, Shan J, Shen J, Xu Y, Zhang Q, et al. Histone deacetylase 3 participates in self-renewal of liver cancer stem cells through histone modification. Cancer Lett 2013;339:60-9.  Back to cited text no. 74
    
75.
Kim SO, Choi BT, Choi IW, Cheong J, Kim GY, Kwon TK, 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 Rep 2009;42:655-60.  Back to cited text no. 75
    
76.
Liu YL, Yang PM, Shun CT, Wu MS, Weng JR, Chen CC. Autophagy potentiates the anti-cancer effects of the histone deacetylase inhibitors in hepatocellular carcinoma. Autophagy 2010;6:1057-65.  Back to cited text no. 76
    
77.
Yeo W, Chung HC, Chan SL, Wang LZ, Lim R, Picus J, et al. 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 2012;30:3361-7.  Back to cited text no. 77
    
78.
Rizvi S, Gores GJ. Emerging molecular therapeutic targets for cholangiocarcinoma. J Hepatol 2017;67:632-44.  Back to cited text no. 78
    
79.
Baradari V, Höpfner M, Huether A, Schuppan D, Scherübl H. Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells. World J Gastroenterol 2007;13:4458-66.  Back to cited text no. 79
    
80.
Yin Y, Zhang M, Dorfman RG, Li Y, Zhao Z, Pan Y, et al. Histone deacetylase 3 overexpression in human cholangiocarcinoma and promotion of cell growth via apoptosis inhibition. Cell Death Dis 2017;8:e2856.  Back to cited text no. 80
    
81.
Asgar MA, Senawong G, Sripa B, Senawong T. Synergistic anticancer effects of cisplatin and histone deacetylase inhibitors (SAHA and TSA) on cholangiocarcinoma cell lines. Int J Oncol 2016;48:409-20.  Back to cited text no. 81
    
82.
Yamaguchi J, Sasaki M, Sato Y, Itatsu K, Harada K, Zen Y, et al. Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma. Cancer Sci 2010;101:355-62.  Back to cited text no. 82
    
83.
Marks PA, Breslow R. Dimethyl sulfoxide to vorinostat: Development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 2007;25:84-90.  Back to cited text no. 83
    
84.
Zhang P, Guo Z, Wu Y, Hu R, Du J, He X, et al. Histone deacetylase inhibitors inhibit the proliferation of gallbladder carcinoma cells by suppressing AKT/mTOR signaling. PLoS One 2015;10:e0136193.  Back to cited text no. 84
    
85.
Kitamura T, Connolly K, Ruffino L, Ajiki T, Lueckgen A, DiGiovanni J, et al. The therapeutic effect of histone deacetylase inhibitor PCI-24781 on gallbladder carcinoma in BK5.erbB2 mice. J Hepatol 2012;57:84-91.  Back to cited text no. 85
    
86.
Ouaïssi M, Sielezneff I, Silvestre R, Sastre B, Bernard JP, Lafontaine JS, et al. High histone deacetylase 7 (HDAC7) expression is significantly associated with adenocarcinomas of the pancreas. Ann Surg Oncol 2008;15:2318-28.  Back to cited text no. 86
    
87.
Bai J, Demirjian A, Sui J, Marasco W, Callery MP. Histone deacetylase inhibitor trichostatin A and proteasome inhibitor PS-341 synergistically induce apoptosis in pancreatic cancer cells. Biochem Biophys Res Commun 2006;348:1245-53.  Back to cited text no. 87
    
88.
Ouaïssi M, Cabral S, Tavares J, da Silva AC, Mathieu Daude F, Mas E, et al. Histone deacetylase (HDAC) encoding gene expression in pancreatic cancer cell lines and cell sensitivity to HDAC inhibitors. Cancer Biol Ther 2008;7:523-31.  Back to cited text no. 88
    
89.
Ouaïssi M, Giger U, Sielezneff I, Pirrò N, Sastre B, Ouaissi A. Rationale for possible targeting of histone deacetylase signaling in cancer diseases with a special reference to pancreatic cancer. J Biomed Biotechnol 2011; 8: 1-8.  Back to cited text no. 89
    
90.
Koutsounas I, Giaginis C, Patsouris E, Theocharis S. Current evidence for histone deacetylase inhibitors in pancreatic cancer. World J Gastroenterol 2013;19:813-28.  Back to cited text no. 90
    
91.
Moore PS, Barbi S, Donadelli M, Costanzo C, Bassi C, Palmieri M, et al. Gene expression profiling after treatment with the histone deacetylase inhibitor trichostatin A reveals altered expression of both pro- and anti-apoptotic genes in pancreatic adenocarcinoma cells. Biochim Biophys Acta 2004;1693:167-76.  Back to cited text no. 91
    
92.
Jakopovic M, Thomas A, Balasubramaniam S, Schrump D, Giaccone G, Bates SE. Targeting the epigenome in lung cancer: Expanding approaches to epigenetic therapy. Front Oncol 2013;3:261.  Back to cited text no. 92
    
93.
Cao LL, Song X, Pei L, Liu L, Wang H, Jia M. Histone deacetylase HDAC1 expression correlates with the progression and prognosis of lung cancer: A meta-analysis. Medicine (Baltimore) 2017;96:e7663.  Back to cited text no. 93
    
94.
Van Den Broeck A, Brambilla E, Moro-Sibilot D, Lantuejoul S, Brambilla C, Eymin B, et al. Loss of histone h4k20 trimethylation occurs in preneoplasia and influences prognosis of non–small cell lung cancer. Clin. Cancer. Res 2008;14:7237-45.  Back to cited text no. 94
    
95.
Bartling B, Hofmann HS, Boettger T, Hansen G, Burdach S, Silber RE, et al. Comparative application of antibody and gene array for expression profiling in human squamous cell lung carcinoma. Lung Cancer 2005;49:145-54.  Back to cited text no. 95
    
96.
Ansari J, Shackelford RE, El-Osta H. Epigenetics in non-small cell lung cancer: From basics to therapeutics. Transl Lung Cancer Res 2016;5:155-71.  Back to cited text no. 96
    
97.
Geng L, Cuneo KC, Fu A, Tu T, Atadja PW, Hallahan DE. Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Cancer Res 2006;66:11298-304.  Back to cited text no. 97
    
98.
Doi S, Soda H, Oka M, Tsurutani J, Kitazaki T, Nakamura Y, et al. The histone deacetylase inhibitor FR901228 induces caspase-dependent apoptosis via the mitochondrial pathway in small cell lung cancer cells. Mol Cancer Ther 2004;3:1397-402.  Back to cited text no. 98
    
99.
Rundall BK, Denlinger CE, Jones DR. Combined histone deacetylase and NF-kappaB inhibition sensitizes non-small cell lung cancer to cell death. Surgery 2004;136:416-25.  Back to cited text no. 99
    
Advanced Biomedical Research
Volume 2019, october
October 2019
Pages 1-12