Histone Deacetylase Enzymes as Potential Drug Targets in Cancer and Parasitic Diseases

Ouaissi, Mehdi; Ouaissi, Ali

doi:https://doi.org/10.1155/JBB/2006/13474

BioMed Research International

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Volume 2006 | Article ID 013474 | https://doi.org/10.1155/JBB/2006/13474

Histone Deacetylase Enzymes as Potential Drug Targets in Cancer and Parasitic Diseases

Mehdi Ouaissi¹and Ali Ouaissi²

Received29 Dec 2005

Revised19 Mar 2006

Accepted22 Mar 2006

Published24 May 2006

Abstract

The elucidation of the mechanisms of transcriptional activation and repression in eukaryotic cells has shed light on the important role of acetylation-deacetylation of histones mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. Another group belonging to the large family of sirtuins (silent information regulators (SIRs)) has an (nicotinamide adenine dinucleotide) NAD+-dependent HDAC activity. Several inhibitors of HDACs (HDIs) have been shown to exert antitumor effects. Interestingly, some of the HDIs exerted a broad spectrum of antiprotozoal activity. The purpose of this review is to analyze some of the current data related to the deacetylase enzymes as a possible target for drug development in cancer and parasitic diseases with special reference to protozoan infections. Given the structural differences among members of this family of enzymes, development of specific inhibitors will not only allow selective therapeutic intervention, but may also provide a powerful tool for functional study of these enzymes.

References

T Kouzarides, “Acetylation: a regulatory modification to rival phosphorylation?” The EMBO Journal, vol. 19, no. 6, pp. 1176–1179, 2000.
View at: Google Scholar
Z W Sun and M Hampsey, “A general requirement for the Sin3-Rpd3 histone deacetylase complex in regulating silencing in Saccharomyces cerevisiae,” Genetics, vol. 152, no. 3, pp. 921–932, 1999.
View at: Google Scholar
J Taunton, C A Hassig, and S L Schreiber, “A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p,” Science, vol. 272, no. 5260, pp. 408–411, 1996.
View at: Google Scholar
D D Leipe and D Landsman, “Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily,” Nucleic Acids Research, vol. 25, no. 18, pp. 3693–3697, 1997.
View at: Google Scholar
S E Rundlett, A A Carmen, R Kobayashi, S Bavykin, B M Turner, and M Grunstein, “HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 25, pp. 14503–14508, 1996.
View at: Google Scholar
A Verdel and S Khochbin, “Identification of a new family of higher eukaryotic histone deacetylases. Coordinate expression of differentiation-dependent chromatin modifiers,” Journal of Biological Chemistry, vol. 274, no. 4, pp. 2440–2445, 1999.
View at: Google Scholar
S G Gray and T J Ekstrom, “The human histone deacetylase family,” Experimental Cell Research, vol. 262, no. 2, pp. 75–83, 2001.
View at: Google Scholar
C M Grozinger, C A Hassig, and S L Schreiber, “Three proteins define a class of human histone deacetylases related to yeast Hda1p,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 9, pp. 4868–4873, 1999.
View at: Google Scholar
X Zhou, P A Marks, R A Rifkind, and V M Richon, “Cloning and characterization of a histone deacetylase, HDAC9,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 19, pp. 10572–10577, 2001.
View at: Google Scholar
C B Brachmann, J M Sherman, S E Devine, E E Cameron, L Pillus, and J D Boeke, “The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability,” Genes & Development, vol. 9, no. 23, pp. 2888–2902, 1995.
View at: Google Scholar
S M Gasser and M M Cockell, “The molecular biology of the SIR proteins,” Gene, vol. 279, no. 1, pp. 1–16, 2001.
View at: Google Scholar
R A Frye, “Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins,” Biochemical and Biophysical Research Communications, vol. 273, no. 2, pp. 793–798, 2000.
View at: Google Scholar
F de Nigris, J Cerutti, C Morelli et al., “Isolation of a SIR-like gene, SIR-T8, that is overexpressed in thyroid carcinoma cell lines and tissues,” British Journal of Cancer, vol. 86, no. 6, pp. 917–923, 2002.
View at: Google Scholar
W D Cress and E Seto, “Histone deacetylases, transcriptional control, and cancer,” Journal of Cellular Physiology, vol. 184, no. 1, pp. 1–16, 2000.
View at: Google Scholar
P S Knoepfler and R N Eisenman, “Sin meets NuRD and other tails of repression,” Cell, vol. 99, no. 5, pp. 447–450, 1999.
View at: Google Scholar
Y Takami and T Nakayama, “N-terminal region, C-terminal region, nuclear export signal, and deacetylation activity of histone deacetylase-3 are essential for the viability of the DT40 chicken B cell line,” Journal of Biological Chemistry, vol. 275, no. 21, pp. 16191–16201, 2000.
View at: Google Scholar
C Underhill, M S Qutob, S-P Yee, and J Torchia, “A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1,” Journal of Biological Chemistry, vol. 275, no. 51, pp. 40463–40470, 2000.
View at: Google Scholar
L Guarente, “Sir2 links chromatin silencing, metabolism, and aging,” Genes & Development, vol. 14, no. 9, pp. 1021–1026, 2000.
View at: Google Scholar
S-J Lin, M Kaeberlein, A A Andalis et al., “Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration,” Nature, vol. 418, no. 6895, pp. 344–348, 2002.
View at: Google Scholar
S W Buck, C M Gallo, and J S Smith, “Diversity in the Sir2 family of protein deacetylases,” Journal of Leukocyte Biology, vol. 75, no. 6, pp. 939–950, 2004.
View at: Google Scholar
M Fulco, R L Schiltz, S Iezzi et al., “Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state,” Molecular Cell, vol. 12, no. 1, pp. 51–62, 2003.
View at: Google Scholar
H Y Cohen, S Lavu, K J Bitterman et al., “Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis,” Molecular Cell, vol. 13, no. 5, pp. 627–638, 2004.
View at: Google Scholar
M C Motta, N Divecha, M Lemieux et al., “Mammalian SIRT1 represses forkhead transcription factors,” Cell, vol. 116, no. 4, pp. 551–563, 2004.
View at: Google Scholar
F Yeung, J E Hoberg, C S Ramsey et al., “Modulation of NF- $\kappa$ B-dependent transcription and cell survival by the SIRT1 deacetylase,” The EMBO Journal, vol. 23, no. 12, pp. 2369–2380, 2004.
View at: Google Scholar
R Kristeleit, L Stimson, P Workman, and W Aherne, “Histone modification enzymes: novel targets for cancer drugs,” Expert Opinion on Emerging Drugs, vol. 9, no. 1, pp. 135–154, 2004.
View at: Google Scholar
M Hiratsuka, T Inoue, T Toda et al., “Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene,” Biochemical and Biophysical Research Communications, vol. 309, no. 3, pp. 558–566, 2003.
View at: Google Scholar
P P Pandolfi, “Histone deacetylases and transcriptional therapy with their inhibitors,” Cancer Chemotherapy and Pharmacology, vol. 48, no. suppl 1, pp. S17–S19, 2001.
View at: Google Scholar
M Kaghad, H Bonnet, A Yang et al., “Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers,” Cell, vol. 90, no. 4, pp. 809–819, 1997.
View at: Google Scholar
L A Donehower, M Harvey, B L Slagle et al., “Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours,” Nature, vol. 356, no. 6366, pp. 215–221, 1992.
View at: Google Scholar
T Rich, R L Allen, and A H Wyllie, “Defying death after DNA damage,” Nature, vol. 407, no. 6805, pp. 777–783, 2000.
View at: Google Scholar
K Nakayama, Y Takebayashi, S Nakayama et al., “Prognostic value of overexpression of p53 in human ovarian carcinoma patients receiving cisplatin,” Cancer Letters, vol. 192, no. 2, pp. 227–235, 2003.
View at: Google Scholar
G Michel, H Auer, L Kemény, A Böcking, and T Ruzicka, “Antioncogene P53 and mitogenic cytokine interleukin-8 aberrantly expressed in psoriatic skin are inversely regulated by the antipsoriatic drug tacrolimus (FK506),” Biochemical Pharmacology, vol. 51, no. 10, pp. 1315–1320, 1996.
View at: Google Scholar
C Prives and J L Manley, “Why is p53 acetylated?” Cell, vol. 107, no. 7, pp. 815–818, 2001.
View at: Google Scholar
H Vaziri, S K Dessain, E N Eaton et al., “ ${\text{hSIR2}}^{{\text{SIRT1}}}$ functions as an NAD-dependent p53 deacetylase,” Cell, vol. 107, no. 2, pp. 149–159, 2001.
View at: Google Scholar
J Luo, A Y Nikolaev, S-I Imai et al., “Negative control of p53 by Sir2 $\alpha$ promotes cell survival under stress,” Cell, vol. 107, no. 2, pp. 137–148, 2001.
View at: Google Scholar
B J North, B L Marshall, M T Borra, J M Denu, and E Verdin, “The human Sir2 ortholog, SIRT2, is an ${\text{NAD}}^ +$ -dependent tubulin deacetylase,” Molecular Cell, vol. 11, no. 2, pp. 437–444, 2003.
View at: Google Scholar
E Hu, Z Chen, T Fredrickson et al., “Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor,” Journal of Biological Chemistry, vol. 275, no. 20, pp. 15254–15264, 2000.
View at: Google Scholar
W-M Yang, Y-L Yao, J-M Sun, J R Davie, and E Seto, “Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family,” Journal of Biological Chemistry, vol. 272, no. 44, pp. 28001–28007, 1997.
View at: Google Scholar
M S Kim, H J Kwon, Y M Lee et al., “Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes,” Nature Medicine, vol. 7, no. 4, pp. 437–443, 2001.
View at: Google Scholar
C P Morales, S E Holt, M Ouellette et al., “Absence of cancer-associated changes in human fibroblasts immortalized with telomerase,” Nature Genetics, vol. 21, no. 1, pp. 115–118, 1999.
View at: Google Scholar
M Karin, Y Cao, F R Greten, and Z-W Li, “NF- $\kappa$ B in cancer: from innocent bystander to major culprit,” Nature Reviews Cancer, vol. 2, no. 4, pp. 301–310, 2002.
View at: Google Scholar
D W Kim, M A Sovak, G Zanieski et al., “Activation of NF- $\kappa$ B/Rel occurs early during neoplastic transformation of mammary cells,” Carcinogenesis, vol. 21, no. 5, pp. 871–879, 2000.
View at: Google Scholar
W Wang, J L Abbruzzese, D B Evans, and P J Chiao, “Overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma is regulated by constitutively activated RelA,” Oncogene, vol. 18, no. 32, pp. 4554–4563, 1999.
View at: Google Scholar
N Mori, Y Nunokawa, Y Yamada, S Ikeda, M Tomonaga, and N Yamamoto, “Expression of human inducible nitric oxide synthase gene in T-cell lines infected with human T-cell leukemia virus type-I and primary adult T-cell leukemia cells,” Blood, vol. 94, no. 8, pp. 2862–2870, 1999.
View at: Google Scholar
P C Cogswell, D C Guttridge, W K Funkhouser, and A S Jr Baldwin, “Selective activation of NF- $\kappa$ B subunits in human breast cancer: potential roles for NF- $\kappa$ B2/p52 and for Bcl-3,” Oncogene, vol. 19, no. 9, pp. 1123–1131, 2000.
View at: Google Scholar
F G Ondrey, G Dong, J Sunwoo et al., “Constitutive activation of transcription factors NF- $\kappa$ B, AP-1, and NF-IL6 in human head and neck squamous cell carcinoma cell lines that express pro-inflammatory and pro-angiogenic cytokines,” Molecular Carcinogenesis, vol. 26, no. 2, pp. 119–129, 1999.
View at: Google Scholar
H Zhong, M J May, E Jimi, and S Ghosh, “The phosphorylation status of nuclear NF- $\kappa$ B determines its association with CBP/p300 or HDAC-1,” Molecular Cell, vol. 9, no. 3, pp. 625–636, 2002.
View at: Google Scholar
L-F Chen, Y Mu, and W C Greene, “Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF- $\kappa$ B,” The EMBO Journal, vol. 21, no. 23, pp. 6539–6548, 2002.
View at: Google Scholar
R Kiernan, V Brès, R WM Ng et al., “Post-activation turn-off of NF- $\kappa$ B-dependent transcription is regulated by acetylation of p65,” Journal of Biological Chemistry, vol. 278, no. 4, pp. 2758–2766, 2003.
View at: Google Scholar
B P Ashburner, S D Westerheide, and A S Jr Baldwin, “The p65 (RelA) subunit of NF- $\kappa$ B interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression,” Molecular and Cellular Biology, vol. 21, no. 20, pp. 7065–7077, 2001.
View at: Google Scholar
L-F Chen, W Fischle, E Verdin, and W C Greene, “Duration of nuclear NF- $\kappa$ B action regulated by reversible acetylation,” Science, vol. 293, no. 5535, pp. 1653–1657, 2001.
View at: Google Scholar
F Yeung, J E Hoberg, C S Ramsey et al., “Modulation of NF- $\kappa$ B-dependent transcription and cell survival by the SIRT1 deacetylase,” The EMBO Journal, vol. 23, no. 12, pp. 2369–2380, 2004.
View at: Google Scholar
J Joseph, N Wajapeyee, and K Somasundaram, “Role of p53 status in chemosensitivity determination of cancer cells against histone deacetylase inhibitor sodium butyrate,” International Journal of Cancer, vol. 115, no. 1, pp. 11–18, 2005.
View at: Google Scholar
T Hirose, Y Sowa, S Takahashi et al., “p53-independent induction of Gadd45 by histone deacetylase inhibitor: coordinate regulation by transcription factors Oct-1 and NF-Y,” Oncogene, vol. 22, no. 49, pp. 7762–7773, 2003.
View at: Google Scholar
R Fenrick and S W Hiebert, “Role of histone deacetylases in acute leukemia,” Journal of Cellular Biochemistry. Supplement, vol. 72, no. S30-31, pp. 194–202, 1998.
View at: Google Scholar
F Grignani, S De Matteis, C Nervi et al., “Fusion proteins of the retinoic acid receptor- $\alpha$ recruit histone deacetylase in promyelocytic leukaemia,” Nature, vol. 391, no. 6669, pp. 815–818, 1998.
View at: Google Scholar
L-Z He, F Guidez, C Tribioli et al., “Distinct interactions of PML-RAR $\alpha$ and PLZF-RAR $\alpha$ with co-repressors determine differential responses to RA in APL,” Nature Genetics, vol. 18, no. 2, pp. 126–135, 1998.
View at: Google Scholar
R J Lin, L Nagy, S Inoue, W Shao, W H Jr Miller, and R M Evans, “Role of the histone deacetylase complex in acute promyelocytic leukaemia,” Nature, vol. 391, no. 6669, pp. 811–814, 1998.
View at: Google Scholar
M R Acharya, A Sparreboom, J Venitz, and W D Figg, “Rational development of histone deacetylase inhibitors as anticancer agents: a review,” Molecular Pharmacology, vol. 68, no. 4, pp. 917–932, 2005.
View at: Google Scholar
F Balkwill and L M Coussens, “Cancer: an inflammatory link,” Nature, vol. 431, no. 7007, pp. 405–406, 2004.
View at: Google Scholar
C Yu, M Rahmani, D Conrad, M Subler, P Dent, and S Grant, “The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/ ${\text{Abl}}^ +$ cells sensitive and resistant to STI571,” Blood, vol. 102, no. 10, pp. 3765–3774, 2003.
View at: Google Scholar
S C Maggio, R R Rosato, L B Kramer et al., “The histone deacetylase inhibitor MS-275 interacts synergistically with fludarabine to induce apoptosis in human leukemia cells,” Cancer Research, vol. 64, no. 7, pp. 2590–2600, 2004.
View at: Google Scholar
K J Bitterman, R M Anderson, H Y Cohen, M Latorre-Esteves, and D A Sinclair, “Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast Sir2 and human SIRT1,” Journal of Biological Chemistry, vol. 277, no. 47, pp. 45099–45107, 2002.
View at: Google Scholar
W B Jonas, C P Rapoza, and W F Blair, “The effect of niacinamide on osteoarthritis: a pilot study,” Inflammation Research, vol. 45, no. 7, pp. 330–334, 1996.
View at: Google Scholar
J HAM Kaanders, L AM Pop, H AM Marres et al., “ARCON: experience in 215 patients with advanced head-and-neck cancer,” International Journal of Radiation Oncology, Biology, Physics, vol. 52, no. 3, pp. 769–778, 2002.
View at: Google Scholar
A Ouaissi and M Ouaissi, “Molecular basis of Trypanosoma cruzi and Leishmania interaction with their host(s): exploitation of immune and defense mechanisms by the parasite leading to persistence and chronicity, features reminiscent of immune system evasion strategies in cancer diseases,” Archivum Immunologiae et Therapiae Experimentalis, vol. 53, no. 2, pp. 102–114, 2005.
View at: Google Scholar
A K Ingram and D Horn, “Histone deacetylases in Trypanosoma brucei two are essential and another is required for normal cell cycle progression,” Molecular Microbiology, vol. 45, no. 1, pp. 89–97, 2002.
View at: Google Scholar
J A García-Salcedo, P Gijón, D P Nolan, P Tebabi, and E Pays, “A chromosomal SIR2 homologue with both histone NAD-dependent ADP-ribosyltransferase and deacetylase activities is involved in DNA repair in Trypanosoma brucei,” The EMBO Journal, vol. 22, no. 21, pp. 5851–5862, 2003.
View at: Google Scholar
M B Joshi, D T Lin, P H Chiang et al., “Molecular cloning and nuclear localization of a histone deacetylase homologue in Plasmodium falciparum,” Molecular and Biochemical Parasitology, vol. 99, no. 1, pp. 11–19, 1999.
View at: Google Scholar
W B Strong and R G Nelson, “Preliminary profile of the Cryptosporidium parvum genome: an expressed sequence tag and genome survey sequence analysis,” Molecular and Biochemical Parasitology, vol. 107, no. 1, pp. 1–32, 2000.
View at: Google Scholar
L H Jr Freitas, R Hernandez-Rivas, S A Ralph et al., “Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites,” Cell, vol. 121, no. 1, pp. 25–36, 2005.
View at: Google Scholar
G Ramakrishnan, C A Gilchrist, H Musa et al., “Histone acetyltransferases and deacetylase in Entamoeba histolytica,” Molecular and Biochemical Parasitology, vol. 138, no. 2, pp. 205–216, 2004.
View at: Google Scholar
B Yahiaoui, M Loyens, A Taibi, R Schöneck, J F Dubremetz, and A Ouaissi, “Characterization of a Leishmania antigen associated with cytoplasmic vesicles resembling endosomal-like structure,” Parasitology, vol. 107, no. pt 5, pp. 497–507, 1993.
View at: Google Scholar
B Yahiaoui, A Taibi, and A Ouaissi, “A Leishmania major protein with extensive homology to silent information regulator 2 of Saccharomyces cerevisiae,” Gene, vol. 169, no. 1, pp. 115–118, 1996.
View at: Google Scholar
B Vergnes, D Sereno, N Madjidian-Sereno, J-L Lemesre, and A Ouaissi, “Cytoplasmic SIR2 homologue overexpression promotes survival of Leishmania parasites by preventing programmed cell death,” Gene, vol. 296, no. 1-2, pp. 139–150, 2002.
View at: Google Scholar
K Zemzoumi, D Sereno, C Francois, E Guilvard, J L Lemesre, and A Ouaissi, “Leishmania major: cell type dependent distribution of a 43 kDa antigen related to silent information regulatory-2 protein family,” Biology of the Cell, vol. 90, no. 3, pp. 239–245, 1998.
View at: Google Scholar
B Vergnes, D Sereno, J Tavares et al., “Targeted disruption of cytosolic SIR2 deacetylase discloses its essential role in Leishmania survival and proliferation,” Gene, vol. 363, pp. 85–96, 2005.
View at: Google Scholar
S J Darkin-Rattray, A M Gurnett, R W Myers et al., “Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 23, pp. 13143–13147, 1996.
View at: Google Scholar
H J Kwon, J-H Kim, M Kim, J-K Lee, W-S Hwang, and D-Y Kim, “Anti-parasitic activity of depudecin on Neospora caninum via the inhibition of histone deacetylase,” Veterinary Parasitology, vol. 112, no. 4, pp. 269–276, 2003.
View at: Google Scholar
B Vergnes, L Vanhille, A Ouaissi, and D Sereno, “Stage-specific antileishmanial activity of an inhibitor of SIR2 histone deacetylase,” Acta Tropica, vol. 94, no. 2, pp. 107–115, 2005.
View at: Google Scholar
M F Murray, “Nicotinamide: an oral antimicrobial agent with activity against both Mycobacterium tuberculosis and human immunodeficiency virus,” Clinical Infectious Diseases, vol. 36, no. 4, pp. 453–460, 2003.
View at: Google Scholar
D Sereno, A Monte Alegre, R Silvestre, B Vergnes, and A Ouaissi, “In vitro antileishmanial activity of Nicotinamide,” Antimicrobial Agents and Chemotherapy, vol. 49, no. 2, pp. 808–812, 2005.
View at: Google Scholar
B S Hall, W Tam, R Sen, and M EA Pereira, “Cell-specific activation of nuclear factor- $\kappa$ B by the parasite Trypanosoma cruzi promotes resistance to intracellular infection,” Molecular Biology of the Cell, vol. 11, no. 1, pp. 153–160, 2000.
View at: Google Scholar
B J North, B L Marshall, M T Borra, J M Denu, and E Verdin, “The human Sir2 ortholog, SIRT2, is an ${\text{NAD}}^ +$ -dependent tubulin deacetylase,” Molecular Cell, vol. 11, no. 2, pp. 437–444, 2003.
View at: Google Scholar

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Copyright © 2006 Mehdi Ouaissi and Ali Ouaissi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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