A Review on Important Histone Acetyltransferase (HAT) Enzymes as Targets for Cancer Therapy

Author(s): Mohammad Ghanbari, Reza Safaralizadeh*, Kiyanoush Mohammadi

Journal Name: Current Cancer Therapy Reviews

Volume 15 , Issue 2 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


At the present time, cancer is one of the most lethal diseases worldwide. There are various factors involved in the development of cancer, including genetic factors, lifestyle, nutrition, and so on. Recent studies have shown that epigenetic factors have a critical role in the initiation and development of tumors. The histone post-translational modifications (PTMs) such as acetylation, methylation, phosphorylation, and other PTMs are important mechanisms that regulate the status of chromatin structure and this regulation leads to the control of gene expression. The histone acetylation is conducted by histone acetyltransferase enzymes (HATs), which are involved in transferring an acetyl group to conserved lysine amino acids of histones and consequently increase gene expression. On the basis of similarity in catalytic domains of HATs, these enzymes are divided into different groups such as families of GNAT, MYST, P300/CBP, SRC/P160, and so on. These enzymes have effective roles in apoptosis, signaling pathways, metastasis, cell cycle, DNA repair and other related mechanisms deregulated in cancer. Abnormal activation of HATs leads to uncontrolled amplification of cells and incidence of malignancy signs. This indicates that HAT might be an important target for effective cancer treatments, and hence there would be a need for further studies and designing of therapeutic drugs on this basis. In this study, we have reviewed the important roles of HATs in different human malignancies.

Keywords: Epigenetics, histone modification, histone acetyltransferase, cancer, drug design, post-translational modifications.

Kornberg RD, Lorch Y. Twenty-five wears of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 1999; 98(3): 285-94.
Lee KK, Workman JL. Histone acetyltransferase complexes: One size doesn’t fit all. Nat Rev Mol Cell Biol 2007; 8(4): 284-95.
Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res 2011; 21(3): 381-95.
Struhl K. Histone acetylation and transcriptional regulatory mechanisms. Genes Dev 1998; 12(5): 599-606.
Fukuda H, Sano N, Muto S, et al. Simple histone acetylation plays a complex role in the regulation of gene expression. Brief Funct Genomics Proteomics 2006; 5(3): 190-208.
Hodawadekar SC, Marmorstein R. Chemistry of acetyl transfer by histone modifying enzymes: Structure, mechanism and implications for effector design. Oncogene 2007; 26(37): 5528-40.
Seidel C, Schnekenburger M, Dicato M, et al. Histone deacetylase modulators provided by Mother Nature. Genes Nutr 2012; 7(3): 357-67.
Sterner DE, Berger SL. Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 2000; 64(2): 435-59.
Xue L, Hou J, Wang Q, et al. RNAi screening identifies HAT1 as a potential drug target in esophageal squamous cell carcinoma. Int J Clin Exp Pathol 2014; 7(7): 3898-907.
Pogribny IP, Tryndyak VP, Muskhelishvili L, et al. Methyl deficiency, alterations in global histone modifications and carcinogenesis. J Nutr 2007; 137(1)(Suppl.): 216S-22S.
Sundar IK, Rahman I. Gene expression profiling of epigenetic chromatin modification enzymes and histone marks by cigarette smoke: implications for COPD and lung cancer. Am J Physiol Lung Cell Mol Physiol 2016; 311(6): L1245-58.
Kikuchi H, Kuribayashi F, Mimuro H, et al. Lack of GCN5 remarkably enhances the resistance against prolonged endoplasmic reticulum stress-induced apoptosis through up-regulation of Bcl-2 gene expression. Biochem Biophys Res Commun 2015; 463(4): 870-5.
Li T, Su L, Lei Y, et al. DDIT3 and KAT2A proteins regulate TNFRSF10A and TNFRSF10B expression in endoplasmic reticulum stress-mediated apoptosis in human lung cancer cells. J Biol Chem 2015; 290(17): 11108-18.
Trisciuoglio D, Ragazzoni Y, Pelosi A, et al. CPTH6, a thiazole derivative, induces histone hypoacetylation and apoptosis in human leukemia cells. Clin Cancer Res 2012; 18(2): 475-86.
Gaupel AC, Begley TJ, Tenniswood M. Gcn5 modulates the cellular response to oxidative stress and histone deacetylase inhibition. J Cell Biochem 2015; 116(9): 1982-92.
Yin YW, Jin HJ, Zhao W, et al. The Histone acetyltransferase GCN5 expression is elevated and regulated by c-Myc and E2F1 transcription factors in human colon cancer. Gene Expr 2015; 16(4): 187-96.
Chen L, Wei T, Si X, et al. Lysine acetyltransferase GCN5 potentiates the growth of non-small cell lung cancer via promotion of E2F1, cyclin D1, and cyclin E1 expression. J Biol Chem 2013; 288(20): 14510-21.
Holmlund T, Lindberg MJ, Grander D, et al. GCN5 acetylates and regulates the stability of the oncoprotein E2A-PBX1 in acute lymphoblastic leukemia. Leukemia 2013; 27(3): 578-85.
Majaz S, Tong Z, Peng K, et al. Histone acetyltransferase GCN5 promotes human hepatocellular carcinoma progression by enhancing AIB1 expression. Cell Biosci 2016; 6: 47.
Zheng X, Gai X, Ding F, et al. Histone acetyltransferase PCAF up-regulated cell apoptosis in hepatocellular carcinoma via acetylating histone H4 and inactivating AKT signaling. Mol Cancer 2013; 12(1): 96.
Kusio-Kobialka M, Wolanin K, Podszywalow-Bartnicka P, et al. Increased acetylation of lysine 317/320 of p53 caused by BCR-ABL protects from cytoplasmic translocation of p53 and mitochondria-dependent apoptosis in response to DNA damage. Apoptosis 2012; 17(9): 950-63.
Lee KS, Kim DW, Kim JY, et al. Caspase-dependent apoptosis induction by targeted expression of DEK in Drosophila involves histone acetylation inhibition. J Cell Biochem 2008; 103(4): 1283-93.
Wan J, Zhan J, Li S, et al. PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression. Nucleic Acids Res 2015; 43(7): 3591-604.
Li Q, Liu Z, Xu M, et al. PCAF inhibits hepatocellular carcinoma metastasis by inhibition of epithelial-mesenchymal transition by targeting Gli-1. Cancer Lett 2016; 375(1): 190-8.
Tuo H, Zheng X, Tu K, et al. Expression of PCAF in hepatocellular carcinoma and its clinical significance. Xibao Yu Fenzi Mianyixue Zazhi 2013; 29(3): 297-300.
Hirano G, Izumi H, Kidani A, et al. Enhanced expression of PCAF endows apoptosis resistance in cisplatin-resistant cells. Mol Cancer Res 2010; 8(6): 864-72.
Love IM, Sekaric P, Shi D, et al. The histone acetyltransferase PCAF regulates p21 transcription through stress-induced acetylation of histone H3. Cell Cycle 2012; 11(13): 2458-66.
Watts GS, Oshiro MM, Junk DJ, et al. The acetyltransferase p300/CBP-associated factor is a p53 target gene in breast tumor cells. Neoplasia 2004; 6(3): 187-94.
Cai K, Wan Y, Wang Z, et al. C5a promotes the proliferation of human nasopharyngeal carcinoma cells through PCAF-mediated STAT3 acetylation. Oncol Rep 2014; 32(5): 2260-6.
Malatesta M, Steinhauer C, Mohammad F, et al. Histone acetyltransferase PCAF is required for Hedgehog-Gli-dependent transcription and cancer cell proliferation. Cancer Res 2013; 73(20): 6323-33.
Gong AY, Eischeid AN, Xiao J, et al. miR-17-5p targets the p300/CBP-associated factor and modulates androgen receptor transcriptional activity in cultured prostate cancer cells. BMC Cancer 2012; 12: 492.
Safaralizadeh R, Dastmalchi N, Hosseinpourfeizi M, et al. Helicobacter pylori virulence factors in relation to gastrointestinal diseases in Iran. Microb Pathog 2017; 105: 211-7.
Lin Q, Xu H, Chen X, et al. Helicobacter pylori cytotoxin-associated gene A activates tumor necrosis factor-alpha and interleukin-6 in gastric epithelial cells through P300/CBP-associated factor-mediated nuclear factor-kappaB p65 acetylation. Mol Med Rep 2015; 12(4): 6337-45.
Rajendran R, Garva R, Ashour H, et al. Acetylation mediated by the p300/CBP-associated factor determines cellular energy metabolic pathways in cancer. Int J Oncol 2013; 42(6): 1961-72.
Liu Z, Liu Y, Wang H, et al. Patt1, a novel protein acetyltransferase that is highly expressed in liver and downregulated in hepatocellular carcinoma, enhances apoptosis of hepatoma cells. Int J Biochem Cell Biol 2009; 41(12): 2528-37.
Sykes SM, Mellert HS, Holbert MA, et al. Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol Cell 2006; 24(6): 841-51.
Mattera L, Escaffit F, Pillaire MJ, et al. The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways. Oncogene 2009; 28(12): 1506-17.
Liu Z, Liu Y, Wang H, et al. Patt1, a novel protein acetyltransferase that is highly expressed in liver and downregulated in hepatocellular carcinoma, enhances apoptosis of hepatoma cells. Int J Biochem Cell Biol 2009; 41(12): 2528-37.
Feng FL, Yu Y, Liu C, et al. KAT5 silencing induces apoptosis of GBC-SD cells through p38MAPK-mediated upregulation of cleaved Casp9. Int J Clin Exp Pathol 2014; 7(1): 80-91.
Tang Y, Luo J, Zhang W, et al. Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol Cell 2006; 24(6): 827-39.
Fateh A, Feizi MA, Safaralizadeh R, et al. Diagnostic and prognostic value of miR-1287 in colorectal cancer. J Gastrointest Cancer 2016; 47(4): 399-403.
Pandey AK, Zhang Y, Zhang S, et al. TIP60-miR-22 axis as a prognostic marker of breast cancer progression. Oncotarget 2015; 6(38): 41290-306.
Takino T, Nakada M, Li Z, et al. Tip60 regulates MT1-MMP transcription and invasion of glioblastoma cells through NF-kappaB pathway. Clin Exp Metastasis 2016; 33(1): 45-52.
Zhao H, Jin S, Gewirtz AM. The histone acetyltransferase TIP60 interacts with c-Myb and inactivates its transcriptional activity in human leukemia. J Biol Chem 2012; 287(2): 925-34.
Sakuraba K, Yokomizo K, Shirahata A, et al. TIP60 as a potential marker for the malignancy of gastric cancer. Anticancer Res 2011; 31(1): 77-9.
Sakuraba K, Yasuda T, Sakata M, et al. Down-regulation of Tip60 gene as a potential marker for the malignancy of colorectal cancer. Anticancer Res 2009; 29(10): 3953-5.
Shiota M, Yokomizo A, Masubuchi D, et al. Tip60 promotes prostate cancer cell proliferation by translocation of androgen receptor into the nucleus. Prostate 2010; 70(5): 540-54.
Chen G, Cheng Y, Tang Y, et al. Role of Tip60 in human melanoma cell migration, metastasis, and patient survival. J Invest Dermatol 2012; 132(11): 2632-41.
Chinen Y, Taki T, Tsutsumi Y, et al. The leucine twenty homeobox (LEUTX) gene, which lacks a histone acetyltransferase domain, is fused to KAT6A in therapy-related acute myeloid leukemia with t (8;19)(p11;q13). Genes Chromosomes Cancer 2014; 53(4): 299-308.
Katsumoto T, Yoshida N, Kitabayashi I. Roles of the histone acetyltransferase monocytic leukemia zinc finger protein in normal and malignant hematopoiesis. Cancer Sci 2008; 99(8): 1523-7.
Camos M, Esteve J, Jares P, et al. Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression. Cancer Res 2006; 66(14): 6947-54.
Largeot A, Perez-Campo FM, Marinopoulou E, et al. Expression of the MOZ-TIF2 oncoprotein in mice represses senescence. Exp Hematol 2016; 44(4): 231-7.e4.
Rokudai S, Aikawa Y, Tagata Y, et al. Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest. J Biol Chem 2009; 284(1): 237-44.
Rokudai S, Laptenko O, Arnal SM, et al. MOZ increases p53 acetylation and premature senescence through its complex formation with PML. Proc Natl Acad Sci USA 2013; 110(10): 3895-900.
Aikawa Y, Katsumoto T, Zhang P, et al. PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. Nat Med 2010; 16(5): 580-5.
Perez-Campo FM, Costa G, Lie ALM, et al. MOZ-mediated repression of p16(INK) (4) (a) is critical for the self-renewal of neural and hematopoietic stem cells. Stem Cells 2014; 32(6): 1591-601.
Panagopoulos I, Fioretos T, Isaksson M, et al. Fusion of the MORF and CBP genes in acute myeloid leukemia with the t (10;16)(q22;p13). Hum Mol Genet 2001; 10(4): 395-404.
Vizmanos JL, Larrayoz MJ, Lahortiga I, et al. t(10;16)(q22;p13) and MORF-CREBBP fusion is a recurrent event in acute myeloid leukemia. Genes Chromosomes Cancer 2003; 36(4): 402-5.
Panagopoulos I, Gorunova L, Bjerkehagen B, et al. Novel KAT6B-KANSL1 fusion gene identified by RNA sequencing in retroperitoneal leiomyoma with t(10;17)(q22;q21). PLoS One 2015; 10(1)e0117010
Moore SD, Herrick SR, Ince TA, et al. Uterine leiomyomata with t (10; 17) disrupts the histone acetyltransferase MORF. Cancer Res 2004; 64(16): 5570-7.
Guo LL, Yu SY, Li M. Functional analysis of HBO1 in tumor development and inhibitor screening. Int J Mol Med 2016; 38(1): 300-4.
Su J, Wang F, Cai Y, et al. The functional analysis of histone acetyltransferase MOF in tumorigenesis. Int J Mol Sci 2016; 17(1)E99
Li Q, Sun H, Shu Y, et al. hMOF (human males absent on the first), an oncogenic protein of human oral tongue squamous cell carcinoma, targeting EZH2 (enhancer of zeste homolog 2). Cell Prolif 2015; 48(4): 436-42.
Cai M, Hu Z, Liu J, et al. Expression of hMOF in different ovarian tissues and its effects on ovarian cancer prognosis. Oncol Rep 2015; 33(2): 685-92.
Cao L, Zhu L, Yang J, et al. Correlation of low expression of hMOF with clinicopathological features of colorectal carcinoma, gastric cancer and renal cell carcinoma. Int J Oncol 2014; 44(4): 1207-14.
Pfister S, Rea S, Taipale M, et al. The histone acetyltransferase hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in medulloblastoma. Int J Cancer 2008; 122(6): 1207-13.
Qin Y, Chen W, Xiao Y, et al. RFPL3 and CBP synergistically upregulate hTERT activity and promote lung cancer growth. Oncotarget 2015; 6(29): 27130-45.
Zhang LH, Huang Q, Fan XS, et al. Clinicopathological significance of SIRT1 and p300/CBP expression in gastroesophageal junction (GEJ) cancer and the correlation with E-cadherin and MLH1. Pathol Res Pract 2013; 209(10): 611-7.
Ozdag H, Batley SJ, Forsti A, et al. Mutation analysis of CBP and PCAF reveals rare inactivating mutations in cancer cell lines but not in primary tumours. Br J Cancer 2002; 87(10): 1162-5.
Ding L, Chen S, Liu P, et al. CBP loss cooperates with PTEN haploinsufficiency to drive prostate cancer: Implications for epigenetic therapy. Cancer Res 2014; 74(7): 2050-61.
Ono H, Basson MD, Ito H. P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer. Oncotarget 2016; 7(32): 51301-10.
He H, Wang D, Yao H, et al. Transcriptional factors p300 and MRTF-A synergistically enhance the expression of migration-related genes in MCF-7 breast cancer cells. Biochem Biophys Res Commun 2015; 467(4): 813-20.
Zhou J, Zhan S, Tan W, et al. P300 binds to and acetylates MTA2 to promote colorectal cancer cells growth. Biochem Biophys Res Commun 2014; 444(3): 387-90.
Wang SA, Hung CY, Chuang JY, et al. Phosphorylation of p300 increases its protein degradation to enhance the lung cancer progression. Biochim Biophys Acta 2014; 1843(6): 1135-49.
Santer FR, Hoschele PP, Oh SJ, et al. Inhibition of the acetyltransferases p300 and CBP reveals a targetable function for p300 in the survival and invasion pathways of prostate cancer cell lines. Mol Cancer Ther 2011; 10(9): 1644-55.
Kim BK, Im JY, Han G, et al. p300 cooperates with c-Jun and PARP-1 at the p300 binding site to activate RhoB transcription in NSC126188-mediated apoptosis. Biochim Biophys Acta 2014; 1839(5): 364-73.
Iyer NG, Chin SF, Ozdag H, et al. p300 regulates p53-dependent apoptosis after DNA damage in colorectal cancer cells by modulation of PUMA/p21 levels. Proc Natl Acad Sci USA 2004; 101(19): 7386-91.
Kitabayashi I, Aikawa Y, Yokoyama A, et al. Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia with a t(8;22)(p11;q13) chromosome translocation. Leukemia 2001; 15(1): 89-94.
Iyer NG, Xian J, Chin SF, et al. p300 is required for orderly G1/S transition in human cancer cells. Oncogene 2007; 26(1): 21-9.
Iyer NG, Chin SF, Ozdag H, et al. p300 regulates p53-dependent apoptosis after DNA damage in colorectal cancer cells by modulation of PUMA/p21 levels. Proc Natl Acad Sci USA 2004; 101(19): 7386-91.
Debes JD, Sebo TJ, Heemers HV, et al. p300 modulates nuclear morphology in prostate cancer. Cancer Res 2005; 65(3): 708-12.
Ornaghi P, Ballario P, Lena AM, et al. The bromodomain of Gcn5p interacts in vitro with specific residues in the N terminus of histone H4. J Mol Biol 1999; 287: 1-7.
Hassan AH, Prochasson P, Neely KE, et al. Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell 2002; 111(3): 369-79.
Jacobson RH, Ladurner AG, King DS, et al. Structure and function of a human TAFII250 double bromodomain module. Science 2000; 288: 1422-5.
Mujtaba S, He Y, Zeng L, et al. Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation. Mol Cell 2004; 13: 251-63.
Nakamura Y, Umehara T, Nakano K, et al. Crystal structure of the human BRD2 bromodomain. J Biol Chem 2007; 282: 4193-201.
Vollmuth F, Blankenfeldt W, Geyer M, et al. Structures of the dual bromodomains of the P-TEFb-activating protein Brd4 at atomic resolution. J Biol Chem 2009; 284: 36547-56.
Josling GA, Selvarajah SA, Petter M, et al. The role of bromodomain proteins in regulating gene expression. Genes 2012; 3(2): 320-43.
Kingston RE, Narlikar GJ. ATP-dependent remodeling and acetylation as regulators of chromatin fluidity. Genes Dev 1999; 13(18): 2339-52.
Cervoni N, Szyf M. Demethylase activity is directed by histone acetylation. J Biol Chem 2001; 276(44): 40778-87.
Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res 2011; 21(3): 381-95.
Kim CH, Kim JW, Jang SM, et al. The chromodomain-containing histone acetyltransferase TIP60 acts as a code reader, recognizing the epigenetic codes for initiating transcription. Biosci Biotechnol Biochem 2015; 79(4): 532-8.
Huang S, Litt M, Felsenfeld G. Methylation of histone H4 by arginine methyltransferase PRMT1 is essential in vivo for many subsequent histone modifications. Genes Dev 2005; 19(16): 1885-93.
Rossetto D, Avvakumov N, Côté J. Histone phosphorylation: A chromatin modification involved in diverse nuclear events. Epigenetics 2012; 7(10): 1098-108.
Lo WS, Trievel RC, Rojas JR, et al. Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14. Mol Cell 2000; 5: 917-26.
Cheung P, Tanner KG, Cheung WL, et al. Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. Mol Cell 2000; 5: 905-15.
Zhang X, Li B, Rezaeian AH, et al. H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis. Nat Commun 2017; 8: 147-99.
Park SH, Lee SR, Kim BC, et al. Transcriptional regulation of the transforming growth factor beta type II receptor gene by histone acetyltransferase and deacetylase is mediated by NF-Y in human breast cancer cells. J Biol Chem 2002; 277(7): 5168-74.
Xue L, Hou J, Wang Q, et al. RNAi screening identifies HAT1 as a potential drug target in esophageal squamous cell carcinoma. Int J Clin Exp Pathol 2014; 7(7): 3898-907.
Gaughan L, Logan IR, Neal DE, et al. Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation. Nucleic Acids Res 2005; 33(1): 13-26.
Gaughan L, Logan IR, Cook S, et al. Tip60 and histone deacetylase 1 regulate androgen receptoractivity through changes to the acetylation status of the receptor. J Biol Chem 2002; 277(29): 25904-13.
Yang H, Salz T, Zajac-Kaye M, et al. Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigeneticmodulators. FASEB J 2014; 28(10): 4265-79.
Hauser C, Schuettengruber B, Bartl S, et al. Activation of the mouse histone deacetylase 1 gene by cooperative histone phosphorylation and acetylation. Mol Cell Biol 2002; 22(22): 7820-30.
Xiao-Jian S, Na M, Yurong T, et al. The Role of Histone acetyltransferases in normal and malignant hematopoiesis. Front Oncol 2015; 5: 108.
Tscherner M, Stappler E, Hnisz D, et al. The histone acetyltransferase Hat1 facilitates DNA damage repair and morphogenesis in Candida albicans. Mol Microbiol 2012; 86(5): 1197-214.
Ogiwara H, Ui A, Otsuka A, et al. Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors. Oncogene 2011; 30(18): 2135-46.
Ogiwara H, Kohno T. CBP and p300 histone acetyltransferases contribute to homologous recombination by transcriptionally activating the BRCA1 and RAD51 genes. PLoS One 2012; 7(12)e52810
Gajer JM, Furdas SD, Gründer A, et al. Histone acetyltransferase inhibitors block neuroblastoma cell growth in vivo. Oncogenesis 2015; 4e137
Wapenaar H, Dekker FJ. Histone acetyltransferases: Challenges in targeting bi-substrate enzymes. Clin Epigen 2016; 8(1): 59.
Bennett RL, Licht JD. Targeting epigenetics in cancer. Annu Rev Pharmacol Toxicol 2018; 58: 187-207.
Chee CS, Leung D. Targeting epigenetic modifiers for cancer treatments. Curr Pharmacol Rep 2018; 4(4)e1342748
Eckschlager T, Plch J, Stiborova M, et al. Histone deacetylase inhibitors as anticancer drugs. Int J Mol Sci 2017; 18(7): 1414.
Gius D, Cui H, Bradbury CM, 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: 361-71.
Jeong JW, Bae MK, Ahn MY, et al. Regulation and destabilization of HIF-1_ by ARD1-mediated acetylation. Cell 2002; 111: 709-20.
Al-Yacoub N, Fecker LF, Mobs M, et al. Apoptosis induction by SAHA in cutaneous T cell lymphoma cells is related to downregulation of c-FLIP and enhanced TRAIL signaling. J Invest Dermatol 2012; 132(9): 2263-74.
Qian X, Ara G, Mills E, et al. Activity of the histone deacetylase inhibitor belinostat (PXD101) in preclinical models of prostate cancer. Int J Cancer 2008; 122(6): 1400-10.
Furdas SD, Kannan S, Sippl W, et al. Small molecule inhibitors of histone acetyltransferases as epigenetic tools and drug candidates. Arch Pharm (Weinheim) 2012; 345(1): 7-21.
Brown JA, Bourke E, Eriksson LA, et al. Targeting cancer using KAT inhibitors to mimic lethal knockouts. Biochem Soc Trans 2016; 44(4): 979-86.
Yang X, Li L, Liang J, et al. Histone acetyltransferase 1 promotes homologous recombination in DNA repair by facilitating histone turnover. J Biol Chem 2013; 288(25): 18271-82.
Bandyopadhyay K1, Banères JL, Martin A, et al.Spermidinyl-CoA-based HAT inhibitors block DNA repair and provide cancer-specific chemo- and radiosensitization. Cell Cycle 2009; 8(17): 2779-88.
Teng Y, Yu Y, Waters R. The Saccharomyces cerevisiae histone acetyltransferase Gcn5 has a role in the photoreactivation and nucleotide excision repair of UV-induced cyclobutane pyrimidine dimers in the MFA2 gene. J Mol Biol 2002; 316(3): 489-99.
Reuter S, Gupta SC, Park B, et al. Epigenetic changes induced by curcumin and other natural compounds. Genes Nutr 2011; 6(2): 93-108.
Collins HM, Abdelghany MK, Messmer M, et al. Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells. BMC Cancer 2013; 13: 37.
Simó-Riudalbas L, Esteller M. Targeting the histone orthography of cancer: Drugs for writers, erasers and readers. Br J Pharmacol 2015; 172(11): 2716-32.
Khan O, La Thangue NB. HDAC inhibitors in cancer biology: Emerging mechanisms and clinical applications. Immunol Cell Biol 2012; 90(1): 85-94.
Balasubramanyam K, Altaf M, Varier RA, et al. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J Biol Chem 2004; 279(32): 33716-26.
Jagannath S, Dimopoulos MA, Lonial S. Combined proteasome and histone deacetylase inhibition: A promising synergy for patients with relapsed/refractory multiple myeloma. Leuk Res 2010; 34(9): 1111-8.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 20 July, 2018
Page: [120 - 130]
Pages: 11
DOI: 10.2174/1573394714666180720152100
Price: $65

Article Metrics

PDF: 59
PRC: 1