Histone Deacetylases and Their Inhibitors in Cancer Epigenetics
Abstract
:1. Introduction
2. HDAC Classifications
2.1. Class I
2.2. Class II
2.3. Class III
2.4. Class IV
2.5. Similarities in Classes I, II & IV
3. HDAC Inhibition
3.1. Group 1
3.2. Group 2
3.3. Group 3
3.4. Group 4
3.5. Group 5
4. Advances in Studying HDAC/HDACi in Cancer
5. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
- Benedetti, R.; Conte, M.; Altucci, L. Targeting Histone Deacetylases in Diseases: Where Are We? Antioxid. Redox Signal. 2015, 23, 99–126. [Google Scholar] [CrossRef]
- Dawson, M.A.; Kouzarides, T. Cancer Epigenetics: From Mechanism to Therapy. Cell 2012, 150, 12–27. [Google Scholar] [CrossRef] [Green Version]
- Bai, Y.; Li, W.; Wang, T.; Ahmad, D.; Cui, G. Research Advances in the Use of Histone Deacetylase Inhibitors for Epigenetic Targeting of Cancer. Curr. Top. Med. Chem. 2019, 19, 995–1004. [Google Scholar] [CrossRef] [PubMed]
- Lin, H.-Y.; Chen, C.-S.; Lin, S.-P.; Weng, J.-R.; Chen, C.-S. Targeting Histone Deacetylase in Cancer Therapy. Med. Res. Rev. 2006, 26, 397–413. [Google Scholar] [CrossRef] [PubMed]
- Barneda-Zahonero, B.; Parra, M. Histone Deacetylases and Cancer. Mol. Oncol. 2012, 6, 579–589. [Google Scholar] [CrossRef] [PubMed]
- Ell, B.; Kang, Y. Transcriptional Control of Cancer Metastasis. Trends Cell Biol. 2013, 23, 603–611. [Google Scholar] [CrossRef] [PubMed]
- Marks, P.A.; Xu, W.-S. Histone Deacetylase Inhibitors: Potential in Cancer Therapy. J. Cell. Biochem. 2009, 107, 600–608. [Google Scholar] [CrossRef] [PubMed]
- McClure, J.J.; Li, X.; Chou, C.J. Advances and Challenges of HDAC Inhibitors in Cancer Therapeutics. In Advances in Cancer Research; Elsevier: Amsterdam, The Netherlands, 2018; Volume 138, pp. 183–211. [Google Scholar] [CrossRef]
- Ropero, S.; Esteller, M. The Role of Histone Deacetylases (HDACs) in Human Cancer. Mol. Oncol. 2007, 1, 19–25. [Google Scholar] [CrossRef] [PubMed]
- Stengel, K.R.; Hiebert, S.W. Class I HDACs Affect DNA Replication, Repair, and Chromatin Structure: Implications for Cancer Therapy. Antioxid. Redox Signal. 2015, 23, 51–65. [Google Scholar] [CrossRef] [Green Version]
- Heideman, M.R.; Wilting, R.H.; Yanover, E.; Velds, A.; de Jong, J.; Kerkhoven, R.M.; Jacobs, H.; Wessels, L.F.; Dannenberg, J.-H. Dosage-Dependent Tumor Suppression by Histone Deacetylases 1 and 2 through Regulation of c-Myc Collaborating Genes and P53 Function. Blood 2013, 121, 2038–2050. [Google Scholar] [CrossRef]
- Li, X.; Peterson, Y.K.; Inks, E.S.; Himes, R.A.; Li, J.; Zhang, Y.; Kong, X.; Chou, C.J. Class I HDAC Inhibitors Display Different Antitumor Mechanism in Leukemia and Prostatic Cancer Cells Depending on Their P53 Status. J. Med. Chem. 2018, 61, 2589–2603. [Google Scholar] [CrossRef] [PubMed]
- Kwon, Y.; Kim, Y.; Jung, H.; Jeoung, D. Role of HDAC3-MiRNA-CAGE Network in Anti-Cancer Drug-Resistance. Int. J. Mol. Sci. 2018, 20, 51. [Google Scholar] [CrossRef] [PubMed]
- Hanigan, T.W.; Aboukhatwa, S.M.; Taha, T.Y.; Frasor, J.; Petukhov, P.A. Divergent JNK Phosphorylation of HDAC3 in Triple-Negative Breast Cancer Cells Determines HDAC Inhibitor Binding and Selectivity. Cell Chem. Biol. 2017, 24, 1356–1367. [Google Scholar] [CrossRef] [PubMed]
- Vanaja, G.R.; Ramulu, H.G.; Kalle, A.M. Overexpressed HDAC8 in Cervical Cancer Cells Shows Functional Redundancy of Tubulin Deacetylation with HDAC6. Cell Commun. Signal. 2018, 16, 20. [Google Scholar] [CrossRef]
- Riester, D.; Hildmann, C.; Schwienhorst, A. Histone Deacetylase Inhibitors—Turning Epigenic Mechanisms of Gene Regulation into Tools of Therapeutic Intervention in Malignant and Other Diseases. Appl. Microbiol. Biotechnol. 2007, 75, 499–514. [Google Scholar] [CrossRef]
- Qian, D.Z. Targeting Tumor Angiogenesis with Histone Deacetylase Inhibitors: The Hydroxamic Acid Derivative LBH589. Clin. Cancer Res. 2006, 12, 634–642. [Google Scholar] [CrossRef]
- Zhang, T.; Li, J.; Ma, X.; Yang, Y.; Sun, W.; Jin, W.; Wang, L.; He, Y.; Yang, F.; Yi, Z.; et al. Inhibition of HDACs-EphA2 Signaling Axis with WW437 Demonstrates Promising Preclinical Antitumor Activity in Breast Cancer. EBioMedicine 2018, 31, 276–286. [Google Scholar] [CrossRef]
- Hai, Y.; Christianson, D.W. Histone Deacetylase 6 Structure and Molecular Basis of Catalysis and Inhibition. Nat. Chem. Biol. 2016, 12, 741–747. [Google Scholar] [CrossRef]
- Li, G.; Xie, Q.; Yang, Z.; Wang, L.; Zhang, X.; Zuo, B.; Zhang, S.; Yang, A.; Jia, L. Sp1-mediated Epigenetic Dysregulation Dictates HDAC Inhibitor Susceptibility of HER2-overexpressing Breast Cancer. Int. J. Cancer 2019, 145, 3285–3298. [Google Scholar] [CrossRef]
- Zeng, L.-S.; Yang, X.-Z.; Wen, Y.-F.; Mai, S.-J.; Wang, M.-H.; Zhang, M.-Y.; Zheng, X.F.S.; Wang, H.-Y. Overexpressed HDAC4 Is Associated with Poor Survival and Promotes Tumor Progression in Esophageal Carcinoma. Aging 2016, 8, 1236–1248. [Google Scholar] [CrossRef]
- Bottomley, M.J.; Lo Surdo, P.; Di Giovine, P.; Cirillo, A.; Scarpelli, R.; Ferrigno, F.; Jones, P.; Neddermann, P.; De Francesco, R.; Steinkühler, C.; et al. Structural and Functional Analysis of the Human HDAC4 Catalytic Domain Reveals a Regulatory Structural Zinc-Binding Domain. J. Biol. Chem. 2008, 283, 26694–26704. [Google Scholar] [CrossRef] [PubMed]
- Beetch, M.; Lubecka, K.; Shen, K.; Flower, K.; Harandi-Zadeh, S.; Suderman, M.; Flanagan, J.M.; Stefanska, B. Stilbenoid-Mediated Epigenetic Activation of Semaphorin 3A in Breast Cancer Cells Involves Changes in Dynamic Interactions of DNA with DNMT3A and NF1C Transcription Factor. Mol. Nutr. Food Res. 2019, 63, 1801386. [Google Scholar] [CrossRef] [PubMed]
- Cao, C.; Vasilatos, S.N.; Bhargava, R.; Fine, J.L.; Oesterreich, S.; Davidson, N.E.; Huang, Y. Functional Interaction of Histone Deacetylase 5 (HDAC5) and Lysine-Specific Demethylase 1 (LSD1) Promotes Breast Cancer Progression. Oncogene 2017, 36, 133–145. [Google Scholar] [CrossRef] [PubMed]
- Pham, L.; Kaiser, B.; Romsa, A.; Schwarz, T.; Gopalakrishnan, R.; Jensen, E.D.; Mansky, K.C. HDAC3 and HDAC7 Have Opposite Effects on Osteoclast Differentiation. J. Biol. Chem. 2011, 286, 12056–12065. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Song, C.; Zhu, S.; Wu, C.; Kang, J. Histone Deacetylase (HDAC) 10 Suppresses Cervical Cancer Metastasis through Inhibition of Matrix Metalloproteinase (MMP) 2 and 9 Expression. J. Biol. Chem. 2013, 288, 28021–28033. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Farghali, H.; Kemelo, M.K.; Canová, N.K. SIRT1 Modulators in Experimentally Induced Liver Injury. Oxid. Med. Cell. Longev. 2019, 2019, 1–15. [Google Scholar] [CrossRef] [PubMed]
- Bosch-Presegue, L.; Vaquero, A. The Dual Role of Sirtuins in Cancer. Genes Cancer 2011, 2, 648–662. [Google Scholar] [CrossRef]
- Carafa, V.; Rotili, D.; Forgione, M.; Cuomo, F.; Serretiello, E.; Hailu, G.S.; Jarho, E.; Lahtela-Kakkonen, M.; Mai, A.; Altucci, L. Sirtuin Functions and Modulation: From Chemistry to the Clinic. Clin. Epigenet. 2016, 8, 61. [Google Scholar] [CrossRef]
- Carafa, V.; Altucci, L.; Nebbioso, A. Dual Tumor Suppressor and Tumor Promoter Action of Sirtuins in Determining Malignant Phenotype. Front. Pharmacol. 2019, 10, 38. [Google Scholar] [CrossRef] [Green Version]
- Dai, H.; Sinclair, D.A.; Ellis, J.L.; Steegborn, C. Sirtuin Activators and Inhibitors: Promises, Achievements, and Challenges. Pharmacol. Ther. 2018, 188, 140–154. [Google Scholar] [CrossRef]
- Chen, J.; Chan, A.W.H.; To, K.-F.; Chen, W.; Zhang, Z.; Ren, J.; Song, C.; Cheung, Y.-S.; Lai, P.B.S.; Cheng, S.-H.; et al. SIRT2 Overexpression in Hepatocellular Carcinoma Mediates Epithelial to Mesenchymal Transition by Protein Kinase B/Glycogen Synthase Kinase-3β/β-Catenin Signaling. Hepatology 2013, 57, 2287–2298. [Google Scholar] [CrossRef] [PubMed]
- Chikamatsu, K.; Ishii, H.; Murata, T.; Sakakura, K.; Shino, M.; Toyoda, M.; Takahashi, K.; Masuyama, K. Alteration of Cancer Stem Cell-like Phenotype by Histone Deacetylase Inhibitors in Squamous Cell Carcinoma of the Head and Neck. Cancer Sci. 2013, 104, 1468–1475. [Google Scholar] [CrossRef]
- McGlynn, L.M.; Zino, S.; MacDonald, A.I.; Curle, J.; Reilly, J.E.; Mohammed, Z.M.A.; McMillan, D.C.; Mallon, E.; Payne, A.P.; Edwards, J.; et al. SIRT2: Tumour Suppressor or Tumour Promoter in Operable Breast Cancer? Eur. J. Cancer 2014, 50, 290–301. [Google Scholar] [CrossRef] [PubMed]
- Huang, S.; Zhao, Z.; Tang, D.; Zhou, Q.; Li, Y.; Zhou, L.; Yin, Y.; Wang, Y.; Pan, Y.; Dorfman, R.G.; et al. Downregulation of SIRT2 Inhibits Invasion of Hepatocellular Carcinoma by Inhibiting Energy Metabolism. Transl. Oncol. 2017, 10, 917–927. [Google Scholar] [CrossRef] [PubMed]
- Inoue, T.; Hiratsuka, M.; Osaki, M.; Oshimura, M. The Molecular Biology of Mammalian SIRT Proteins: SIRT2 Functions on Cell Cycle Regulation. Cell Cycle 2007, 6, 1011–1018. [Google Scholar] [CrossRef] [Green Version]
- Kim, H.-S.; Vassilopoulos, A.; Wang, R.-H.; Lahusen, T.; Xiao, Z.; Xu, X.; Li, C.; Veenstra, T.D.; Li, B.; Yu, H.; et al. SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating APC/C Activity. Cancer Cell 2011, 20, 487–499. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Toubai, T.; Tamaki, H.; Peltier, D.C.; Rossi, C.; Oravecz-Wilson, K.; Liu, C.; Zajac, C.; Wu, J.; Sun, Y.; Fujiwara, H.; et al. Mitochondrial Deacetylase SIRT3 Plays an Important Role in Donor T Cell Responses after Experimental Allogeneic Hematopoietic Transplantation. J. Immunol. 2018, 201, 3443–3455. [Google Scholar] [CrossRef] [PubMed]
- Hu, Y.; Lin, J.; Lin, Y.; Chen, X.; Zhu, G.; Huang, G. Overexpression of SIRT4 Inhibits the Proliferation of Gastric Cancer Cells through Cell Cycle Arrest. Oncol. Lett. 2019, 17, 2171–2176. [Google Scholar] [CrossRef]
- Gong, J.; Wang, H.; Lou, W.; Wang, G.; Tao, H.; Wen, H.; Liu, Y.; Xie, Q. Associations of Sirtuins with Clinicopathological Parameters and Prognosis in Non–Small Cell Lung Cancer. Cancer Manag. Res. 2018, 10, 3341–3356. [Google Scholar] [CrossRef]
- Fu, L.; Dong, Q.; He, J.; Wang, X.; Xing, J.; Wang, E.; Qiu, X.; Li, Q. SIRT4 Inhibits Malignancy Progression of NSCLCs, through Mitochondrial Dynamics Mediated by the ERK-Drp1 Pathway. Oncogene 2017, 36, 2724–2736. [Google Scholar] [CrossRef]
- Chang, L.; Xi, L.; Liu, Y.; Liu, R.; Wu, Z.; Jian, Z. SIRT5 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Targeting E2F1. Mol. Med. Rep. 2017, 17, 342–349. [Google Scholar] [CrossRef] [PubMed]
- Bringman-Rodenbarger, L.R.; Guo, A.H.; Lyssiotis, C.A.; Lombard, D.B. Emerging Roles for SIRT5 in Metabolism and Cancer. Antioxid. Redox Signal. 2018, 28, 677–690. [Google Scholar] [CrossRef] [PubMed]
- Sebastián, C.; Zwaans, B.M.M.; Silberman, D.M.; Gymrek, M.; Goren, A.; Zhong, L.; Ram, O.; Truelove, J.; Guimaraes, A.R.; Toiber, D.; et al. The Histone Deacetylase SIRT6 Is a Tumor Suppressor That Controls Cancer Metabolism. Cell 2012, 151, 1185–1199. [Google Scholar] [CrossRef] [PubMed]
- Blank, M.F.; Grummt, I. The Seven Faces of SIRT7. Transcription 2017, 8, 67–74. [Google Scholar] [CrossRef] [PubMed]
- Shi, H.; Ji, Y.; Zhang, D.; Liu, Y.; Fang, P. MicroRNA-3666-Induced Suppression of SIRT7 Inhibits the Growth of Non-Small Cell Lung Cancer Cells. Oncol. Rep. 2016, 36, 3051–3057. [Google Scholar] [CrossRef] [PubMed]
- Chen, S.; Blank, M.F.; Iyer, A.; Huang, B.; Wang, L.; Grummt, I.; Voit, R. SIRT7-Dependent Deacetylation of the U3-55k Protein Controls Pre-RRNA Processing. Nat. Commun. 2016, 7, 10734. [Google Scholar] [CrossRef]
- Tong, Z.; Wang, Y.; Zhang, X.; Kim, D.D.; Sadhukhan, S.; Hao, Q.; Lin, H. SIRT7 Is Activated by DNA and Deacetylates Histone H3 in the Chromatin Context. ACS Chem. Biol. 2016, 11, 742–747. [Google Scholar] [CrossRef] [Green Version]
- Haider, R.; Massa, F.; Kaminski, L.; Clavel, S.; Djabari, Z.; Robert, G.; Laurent, K.; Michiels, J.-F.; Durand, M.; Ricci, J.-E.; et al. Sirtuin 7: A New Marker of Aggressiveness in Prostate Cancer. Oncotarget 2017, 8, 77309. [Google Scholar] [CrossRef]
- Kim, J.K.; Noh, J.H.; Jung, K.H.; Eun, J.W.; Bae, H.J.; Kim, M.G.; Chang, Y.G.; Shen, Q.; Park, W.S.; Lee, J.Y.; et al. Sirtuin7 Oncogenic Potential in Human Hepatocellular Carcinoma and Its Regulation by the Tumor Suppressors MiR-125a-5p and MiR-125b. Hepatology 2013, 57, 1055–1067. [Google Scholar] [CrossRef]
- Wei, W.; Jing, Z.X.; Ke, Z.; Yi, P. Sirtuin 7 Plays an Oncogenic Role in Human Osteosarcoma via Downregulating CDC4 Expression. Am. J. Cancer Res. 2017, 7, 1788–1803. [Google Scholar]
- Bagchi, R.A.; Ferguson, B.S.; Stratton, M.S.; Hu, T.; Cavasin, M.A.; Sun, L.; Lin, Y.-H.; Liu, D.; Londono, P.; Song, K.; et al. HDAC11 Suppresses the Thermogenic Program of Adipose Tissue via BRD2. JCI Insight 2018, 3. [Google Scholar] [CrossRef] [PubMed]
- Moreno-Yruela, C.; Galleano, I.; Madsen, A.S.; Olsen, C.A. Histone Deacetylase 11 Is an ε-N-Myristoyllysine Hydrolase. Cell Chem. Biol. 2018, 25, 849–856. [Google Scholar] [CrossRef] [PubMed]
- Cao, J.; Sun, L.; Aramsangtienchai, P.; Spiegelman, N.A.; Zhang, X.; Huang, W.; Seto, E.; Lin, H. HDAC11 Regulates Type I Interferon Signaling through Defatty-Acylation of SHMT2. Proc. Natl. Acad. Sci. USA 2019, 116, 5487–5492. [Google Scholar] [CrossRef] [PubMed]
- Di Pompo, G.; Salerno, M.; Rotili, D.; Valente, S.; Zwergel, C.; Avnet, S.; Lattanzi, G.; Baldini, N.; Mai, A. Novel Histone Deacetylase Inhibitors Induce Growth Arrest, Apoptosis, and Differentiation in Sarcoma Cancer Stem Cells. J. Med. Chem. 2015, 58, 4073–4079. [Google Scholar] [CrossRef]
- Dokmanovic, M.; Clarke, C.; Marks, P.A. Histone Deacetylase Inhibitors: Overview and Perspectives. Mol. Cancer Res. 2007, 5, 981–989. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fu, H.; Cheng, L.; Jin, Y.; Cheng, L.; Liu, M.; Chen, L. MAPK Inhibitors Enhance HDAC Inhibitor-Induced Redifferentiation in Papillary Thyroid Cancer Cells Harboring BRAFV600E: An In Vitro Study. Mol. Ther. Oncolytics 2019, 12, 235–245. [Google Scholar] [CrossRef] [Green Version]
- Huang, M.; Zhang, J.; Yan, C.; Li, X.; Zhang, J.; Ling, R. Small Molecule HDAC Inhibitors: Promising Agents for Breast Cancer Treatment. Bioorganic Chem. 2019, 91, 103184. [Google Scholar] [CrossRef]
- Janssens, N.; Janicot, M.; Perera, T. The Wnt-Dependent Signaling Pathways as Target in Oncology Drug Discovery. Investig. New Drugs 2006, 24, 263–280. [Google Scholar] [CrossRef]
- Licciardi, P.V.; Ververis, K.; Hiong, A.; Karagiannis, T.C. Histone Deacetylase Inhibitors (HDACIs): Multitargeted Anticancer Agents. Biol. Targets Ther. 2013, 7, 47. [Google Scholar] [CrossRef]
- Chueh, A.C.; Tse, J.W.T.; Tögel, L.; Mariadason, J.M. Mechanisms of Histone Deacetylase Inhibitor-Regulated Gene Expression in Cancer Cells. Antioxid. Redox Signal. 2015, 23, 66–84. [Google Scholar] [CrossRef] [Green Version]
- Conte, M.; De Palma, R.; Altucci, L. HDAC Inhibitors as Epigenetic Regulators for Cancer Immunotherapy. Int. J. Biochem. Cell Biol. 2018, 98, 65–74. [Google Scholar] [CrossRef] [PubMed]
- McDonald, A.J.; Curt, K.M.; Patel, R.P.; Kozlowski, H.; Sackett, D.L.; Robey, R.W.; Gottesman, M.M.; Bates, S.E. Targeting Mitochondrial Hexokinases Increases Efficacy of Histone Deacetylase Inhibitors in Solid Tumor Models. Exp. Cell Res. 2019, 375, 106–112. [Google Scholar] [CrossRef] [PubMed]
- Banerjee, A.; Mahata, B.; Dhir, A.; Mandal, T.K.; Biswas, K. Elevated Histone H3 Acetylation and Loss of the Sp1–HDAC1 Complex de-Repress the GM2-Synthase Gene in Renal Cell Carcinoma. J. Biol. Chem. 2019, 294, 1005–1018. [Google Scholar] [CrossRef] [PubMed]
- Merarchi, M.; Sethi, G.; Shanmugam, M.; Fan, L.; Arfuso, F.; Ahn, K. Role of Natural Products in Modulating Histone Deacetylases in Cancer. Molecules 2019, 24, 1047. [Google Scholar] [CrossRef] [PubMed]
- Khan, O.; La Thangue, N.B. HDAC Inhibitors in Cancer Biology: Emerging Mechanisms and Clinical Applications. Immunol. Cell Biol. 2012, 90, 85–94. [Google Scholar] [CrossRef]
- Aztopal, N.; Erkisa, M.; Erturk, E.; Ulukaya, E.; Tokullugil, A.H.; Ari, F. Valproic Acid, a Histone Deacetylase Inhibitor, Induces Apoptosis in Breast Cancer Stem Cells. Chem. Biol. Interact. 2018, 280, 51–58. [Google Scholar] [CrossRef] [PubMed]
- Khan, O.; Fotheringham, S.; Wood, V.; Stimson, L.; Zhang, C.; Pezzella, F.; Duvic, M.; Kerr, D.J.; La Thangue, N.B. HR23B Is a Biomarker for Tumor Sensitivity to HDAC Inhibitor-Based Therapy. Proc. Natl. Acad. Sci. USA 2010, 107, 6532–6537. [Google Scholar] [CrossRef]
- Grant, S.; Easley, C.; Kirkpatrick, P. Vorinostat. Nat. Rev. Drug Discov. 2007, 6, 21. [Google Scholar] [CrossRef]
- West, A.C.; Johnstone, R.W. New and Emerging HDAC Inhibitors for Cancer Treatment. J. Clin. Investig. 2014, 124, 30–39. [Google Scholar] [CrossRef]
- McClure, J.J.; Zhang, C.; Inks, E.S.; Peterson, Y.K.; Li, J.; Chou, C.J. Development of Allosteric Hydrazide-Containing Class I Histone Deacetylase Inhibitors for Use in Acute Myeloid Leukemia. J. Med. Chem. 2016, 59, 9942–9959. [Google Scholar] [CrossRef] [Green Version]
- Wieduwilt, M.J.; Pawlowska, N.; Thomas, S.; Olin, R.; Logan, A.C.; Damon, L.E.; Martin, T.; Kang, M.; Sayre, P.H.; Boyer, W.; et al. Histone Deacetylase Inhibition with Panobinostat Combined with Intensive Induction Chemotherapy in Older Patients with Acute Myeloid Leukemia: Phase I Study Results. Clin. Cancer Res. 2019, 25. [Google Scholar] [CrossRef] [PubMed]
- Grasso, C.S.; Tang, Y.; Truffaux, N.; Berlow, N.E.; Liu, L.; Debily, M.-A.; Quist, M.J.; Davis, L.E.; Huang, E.C.; Woo, P.J.; et al. Functionally Defined Therapeutic Targets in Diffuse Intrinsic Pontine Glioma. Nat. Med. 2015, 21, 555–559. [Google Scholar] [CrossRef] [PubMed]
- Schlenk, R.F.; Krauter, J.; Raffoux, E.; Kreuzer, K.-A.; Schaich, M.; Noens, L.; Pabst, T.; Vusirikala, M.; Bouscary, D.; Spencer, A.; et al. Panobinostat Monotherapy and Combination Therapy in Patients with Acute Myeloid Leukemia: Results from Two Clinical Trials. Haematologica 2018, 103, e25–e28. [Google Scholar] [CrossRef] [PubMed]
- Plumb, J.A.; Finn, P.W.; Williams, R.J.; Bandara, M.J.; Romero, M.R.; Watkins, C.J.; La Thangue, N.B.; Brown, R. Pharmacodynamic Response and Inhibition of Growth of Human Tumor Xenografts by the Novel Histone Deacetylase Inhibitor PXD101. Mol. Cancer Ther. 2003, 2, 721–728. [Google Scholar] [PubMed]
- Bolden, J.E.; Shi, W.; Jankowski, K.; Kan, C.-Y.; Cluse, L.; Martin, B.P.; MacKenzie, K.L.; Smyth, G.K.; Johnstone, R.W. HDAC Inhibitors Induce Tumor-Cell-Selective pro-Apoptotic Transcriptional Responses. Cell Death Dis. 2013, 4, e519. [Google Scholar] [CrossRef]
- Heers, H.; Stanislaw, J.; Harrelson, J.; Lee, M.W. Valproic Acid as an Adjunctive Therapeutic Agent for the Treatment of Breast Cancer. Eur. J. Pharmacol. 2018, 835, 61–74. [Google Scholar] [CrossRef]
- Tsai, H.-C.; Wei, K.-C.; Tsai, C.-N.; Huang, Y.-C.; Chen, P.-Y.; Chen, S.-M.; Lu, Y.-J.; Lee, S.-T. Effect of Valproic Acid on the Outcome of Glioblastoma Multiforme. Br. J. Neurosurg. 2012, 26, 347–354. [Google Scholar] [CrossRef]
- Makarević, J.; Rutz, J.; Juengel, E.; Maxeiner, S.; Mani, J.; Vallo, S.; Tsaur, I.; Roos, F.; Chun, F.; Blaheta, R. HDAC Inhibition Counteracts Metastatic Re-Activation of Prostate Cancer Cells Induced by Chronic MTOR Suppression. Cells 2018, 7, 129. [Google Scholar] [CrossRef]
- Ferrari, P.; Nicolini, A. Overcoming Endocrine Resistance in Breast Cancer. In Oncogenomics; Elsevier: Amsterdam, The Netherlands, 2019; pp. 393–422. [Google Scholar] [CrossRef]
- Connolly, R.M.; Rudek, M.A.; Piekarz, R. Entinostat: A Promising Treatment Option for Patients with Advanced Breast Cancer. Future Oncol. Lond. Engl. 2017, 13, 1137–1148. [Google Scholar] [CrossRef]
- Chen, Y.; Wang, X.; Xiang, W.; He, L.; Tang, M.; Wang, F.; Wang, T.; Yang, Z.; Yi, Y.; Wang, H.; et al. Development of Purine-Based Hydroxamic Acid Derivatives: Potent Histone Deacetylase Inhibitors with Marked in Vitro and in Vivo Antitumor Activities. J. Med. Chem. 2016, 59, 5488–5504. [Google Scholar] [CrossRef]
- Barbarotta, L.; Hurley, K. Romidepsin for the Treatment of Peripheral T-Cell Lymphoma. J. Adv. Pract. Oncol. 2015, 6, 22–36. [Google Scholar] [PubMed]
- Foss, F.M.; Zinzani, P.L.; Vose, J.M.; Gascoyne, R.D.; Rosen, S.T.; Tobinai, K. Peripheral T-Cell Lymphoma. Blood 2011, 117, 6756–6767. [Google Scholar] [CrossRef] [PubMed]
- Smolewski, P.; Robak, T. The Discovery and Development of Romidepsin for the Treatment of T-Cell Lymphoma. Expert Opin. Drug Discov. 2017, 12, 859–873. [Google Scholar] [CrossRef] [PubMed]
- Sun, W.-J.; Huang, H.; He, B.; Hu, D.-H.; Li, P.-H.; Yu, Y.-J.; Zhou, X.-H.; Lv, Z.; Zhou, L.; Hu, T.-Y.; et al. Romidepsin Induces G2/M Phase Arrest via Erk/Cdc25C/Cdc2/CyclinB Pathway and Apoptosis Induction through JNK/c-Jun/Caspase3 Pathway in Hepatocellular Carcinoma Cells. Biochem. Pharmacol. 2017, 127, 90–100. [Google Scholar] [CrossRef] [PubMed]
- Yoon, Y.K.; Ali, M.A.; Wei, A.C.; Choon, T.S.; Osman, H.; Parang, K.; Shirazi, A.N. Synthesis and Evaluation of Novel Benzimidazole Derivatives as Sirtuin Inhibitors with Antitumor Activities. Bioorg. Med. Chem. 2014, 22, 703–710. [Google Scholar] [CrossRef]
- Mahajan, S.S.; Scian, M.; Sripathy, S.; Posakony, J.; Lao, U.; Loe, T.K.; Leko, V.; Thalhofer, A.; Schuler, A.D.; Bedalov, A.; et al. Development of Pyrazolone and Isoxazol-5-One Cambinol Analogues as Sirtuin Inhibitors. J. Med. Chem. 2014, 57, 3283–3294. [Google Scholar] [CrossRef]
- Tan, Y.J.; Lee, Y.T.; Yeong, K.Y.; Petersen, S.H.; Kono, K.; Tan, S.C.; Oon, C.E. Anticancer Activities of a Benzimidazole Compound through Sirtuin Inhibition in Colorectal Cancer. Future Med. Chem. 2018, 10, 2039–2057. [Google Scholar] [CrossRef]
- Sultana, F.; Manasa, K.L.; Shaik, S.P.; Bonam, S.R.; Kamal, A. Zinc Dependent Histone Deacetylase Inhibitors in Cancer Therapeutics: Recent Update. Curr. Med. Chem. 2018, 25. [Google Scholar] [CrossRef]
- Monga, M.; Sausville, E. Developmental Therapeutics Program at the NCI: Molecular Target and Drug Discovery Process. Leukemia 2002, 16, 520–526. [Google Scholar] [CrossRef]
- Hsu, K.-C.; Liu, C.-Y.; Lin, T.E.; Hsieh, J.-H.; Sung, T.-Y.; Tseng, H.-J.; Yang, J.-M.; Huang, W.-J. Novel Class IIa-Selective Histone Deacetylase Inhibitors Discovered Using an in Silico Virtual Screening Approach. Sci. Rep. 2017, 7, 3228. [Google Scholar] [CrossRef] [Green Version]
- Arnold, K.; Bordoli, L.; Kopp, J.; Schwede, T. The SWISS-MODEL Workspace: A Web-Based Environment for Protein Structure Homology Modelling. Bioinformatics 2006, 22, 195–201. [Google Scholar] [CrossRef] [PubMed]
Class: | Localization: | HDAC | Characteristics: | Activity in Cancer: | Refs. |
---|---|---|---|---|---|
I* | nucleus | 1 | N-terminus catalytic domain | Overexpressed in tissues from breast, gastric, pancreas, lungs, cervical and prostate cancers | [10,11,12] |
2 | [10,11,12] | ||||
3 | Interaction with HDAC4, 5, 7 & cancer-associated genes (CAGE) | [13,14] | |||
8 | Interaction with HDAC4, 5, 7 | [15] | |||
IIa* | cytoplasm & nucleus | 4 | C-terminus catalytic domain combines with HDAC3 via N-CoR, catalytic activity structurally regulates access to the Zn2+ binding domain | Suppresses p21; overexpressed in breast, colon, ovarian and gastric cancers | [22] |
5 | Interacts with lysine-specific demethylase 1 | Markers in medulloblastomas & breast cancer | [24] | ||
7 | C-terminus activity; non-deacetylase dependent | Overexpression in pancreatic cancer & acute lymphoblastic leukemia | [11,22,25] | ||
9 | Splice variants with catalytic domain on its C-terminus | Markers in medulloblastomas | [25] | ||
IIb* | cytoplasm & nucleus | 6 | 2 tandem catalytic domains | Highly expressed in breast cancer; stage indicator | [16,20] |
cytoplasm | 10 | Catalytic domain activity at N-terminus & C-terminus leucine rich domain (LRD) | Cervical cancer as a metastasis suppressor | [21] | |
III** | nucleus | SIRT1 | Lys382 residue deacetylate of H1, H3, and H4; C-terminus p53 acetylation regulator | Tumor suppressor in retinoblastoma | [27,28,29,30,31] |
SIRT6 | Glycolysis regulator in cancer cells | Tumor suppressor in retinoblastoma | |||
SIRT7 | Deacetylates lysine 18 residue of H3; succinyls activity | Ovarian, colorectal, osteosarcoma, prostate, hepatocellular, breast & non-small cell lung | [45,46,47,48,49,50,51] | ||
cytoplasm | SIRT2 | Deacetylating α-tubulin | Tumor suppressor; ovarian, breast, leukemia, neuroblastoma, pancreatic & hepatocellular | [32,33,34,35,36,37] | |
mitochondria | SIRT3 | Transcription factor regulation via deacetylation | Transcription factor regulation in breast cancer | [38] | |
SIRT4 | Glutamate dehydrogenase and poly ADP-ribose polymerase (PARP) inhibition | Tumor suppressor in gastric cancers | [39,40,41] | ||
SIRT5 | Promotes cell proliferation | Hepatocellular carcinoma | [44] | ||
IV* | nucleus | 11 | Interacts with HDAC1 & 2; defatty-acylate substrate activity | Overexpressed in Hodgkin’s lymphoma | [5,52,53,54] |
Class: | HDACi | Characteristics: | Activity in Cancer: | Drug Name: | Refs. |
---|---|---|---|---|---|
I | suberoylanilide hydroxamic acid (Vorinostat) | Inhibits HDAC class I & II via Zn2+ ion interactions | Induces apoptosis in T-cell lymphomas, thymoma & liver | Zolinza | [65,66,67,68,69,70] |
Panobinostat | Farydak | [71,72,73,74] | |||
Belinostat | Beleodaq | [60,75] | |||
valproic acis (VPA) | N/A | [67,76,77,78,79] | |||
II | Entinostat | Synergistic enhancement obsevered with other anticancer compounds due to short-chained fatty acid | Lymphocytic leukemia, acute myeloid leukemia, melanoma & glioblastoma | N/A | [60,80,81,82] |
III | Apicidin | Benzamide group; inhibits HDAC class I & II; selective autophagy inducer | Antitumor promoter in hormone receptor breast cancer | N/A | [83] |
IV | Romidepsin | Bicyclic peptides; inhibit HDAC class I & II; triggers the accumulation of acetylated histones to induce apoptosis in cancer cells | Colorectal, renal, breast cancers & T-cell lymphoma | Istodax | [83,84,85,86] |
V | Cambinol | Inhibits SIRT1 and 2 by induced hyperacetylation of p53 | Inhibits SIRT1 and 2 by inducing the hyperacetylation of p53 | N/A | [29,31,27,88,89] |
© 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Hassell, K.N. Histone Deacetylases and Their Inhibitors in Cancer Epigenetics. Diseases 2019, 7, 57. https://doi.org/10.3390/diseases7040057
Hassell KN. Histone Deacetylases and Their Inhibitors in Cancer Epigenetics. Diseases. 2019; 7(4):57. https://doi.org/10.3390/diseases7040057
Chicago/Turabian StyleHassell, Kelly N. 2019. "Histone Deacetylases and Their Inhibitors in Cancer Epigenetics" Diseases 7, no. 4: 57. https://doi.org/10.3390/diseases7040057
APA StyleHassell, K. N. (2019). Histone Deacetylases and Their Inhibitors in Cancer Epigenetics. Diseases, 7(4), 57. https://doi.org/10.3390/diseases7040057