Synopsis
The process of transcription is tightly controlled by the acetylation and deacetylation of histone proteins. Histone acetyltransferases (HATs) enhance the acetylation of histone proteins, thereby causing gene activation, while histone deacetylases (HDACs) show the opposite effect. The histone proteins are no longer only inert structures but are instructive scaffolds governing gene expression programs by responding to a plethora of internal and external cues. HDAC overexpression plays a critical role in gene dysregulation which ends in life-threatening disorders including cancer. HDAC inhibitors restrain HDACs and are the newly emerging anticancer drug candidates that have the potential to modulate both epigenetic and non-epigenetic pathways. HDAC inhibitors belong to diverse groups and have showed success to a greater extent against diverse diseases like cancer, acquired immune deficiency syndrome (AIDS), diabetes, neurodegeneration, etc. HDAC inhibitors influence only 2 % of...
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References
Arnold NB, Arkus N, Gunn J, Korc M (2007) The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces growth inhibition and enhances gemcitabine-induced cell death in pancreatic cancer. Clin Cancer Res 13:18–26
Baradari V, Huether A, Hopfner M, Schuppan D, Scherubl H (2006) Antiproliferative and proapoptotic effects of histone deacetylase inhibitors on gastrointestinal neuroendocrine tumor cells. Endocr Relat Cancer 13:1237–1250
Bergadà L, Sorolla A, Yeramian A, Eritja N, Mirantes C, Matias-Guiu X et al (2013) Combination of Vorinostat and caspase-8 inhibition exhibits high anti-tumoral activity on endometrial cancer cells. Mol Oncol 7:763–775
Bolden JE, Peart MJ, Johnstone RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5:769–784
Bracker TU, Sommer A, Fichtner I, Faus H, Haendler B, Hess-Stumpp H (2009) Efficacy of MS-275, a selective inhibitor of class I histone deacetylases, in human colon cancer models. Int J Oncol 35:909–920
Butler LM, Zhou X, Xu WS, Scher HI, Rifkind RA, Marks PA et al (2002) The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Proc Natl Acad Sci U S A 99:11700–11705
Chen X, Radany EH, Wong P, Ma S, Wu K, Wang B et al (2013) Suberoylanilide hydroxamic acid induces hypersensitivity to radiation therapy in acute myelogenous leukemia cells expressing constitutively active FLT3 mutants. PLoS One 8:e84515
de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370:737–749
Dokmanovic M, Clarke C, Marks PA (2007) Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 5:981–989
Grunstein M (1997) Histone acetylation in chromatin structure and transcription. Nature 389:349–352
Kumagai T, Wakimoto N, Yin D, Gery S, Kawamata N, Takai N et al (2007) Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (Vorinostat, SAHA) profoundly inhibits the growth of human pancreatic cancer cells. Int J Cancer 121:656–665
Lakshmikanthan V, Kaddour-Djebbar I, Lewis RW, Kumar MV (2006) SAHA-sensitized prostate cancer cells to TNFalpha-related apoptosis-inducing ligand (TRAIL): mechanisms leading to synergistic apoptosis. Int J Cancer 119:221–228
Luo RX, Dean DC (1999) Chromatin remodeling and transcriptional regulation. J Natl Cancer Inst 91:1288–1294
Ouaissi M, Sielezneff I, Silvestre R, Sastre B, Bernard JP, Lafontaine JS et al (2008) High histone deacetylase 7 (HDAC7) expression is significantly associated with adenocarcinomas of the pancreas. Ann Surg Oncol 15:2318–2328
Qu W, Kang Y-d, Zhou M-s, Fu L-l, Hua Z-h, Wang L-m (2010) Experimental study on inhibitory effects of histone deacetylase inhibitor MS-275 and TSA on bladder cancer cells. Urol Oncol 28:648–654
Srivastava RK, Kurzrock R, Shankar S (2010) MS-275 sensitizes TRAIL-resistant breast cancer cells, inhibits angiogenesis and metastasis, and reverses epithelial-mesenchymal transition in vivo. Mol Cancer Ther 9:3254–3266
Stark K, Burger A, Wu J, Shelton P, Polin L, Li J (2013) Reactivation of estrogen receptor alpha by vorinostat sensitizes mesenchymal-like triple-negative breast cancer to aminoflavone, a ligand of the aryl hydrocarbon receptor. PLoS One 8:e74525
Takai N, Ueda T, Nishida M, Nasu K, Narahara H (2006) Anticancer activity of MS-275, a novel histone deacetylase inhibitor, against human endometrial cancer cells. Anticancer Res 26:939–945
Xu J, Zhou JY, Wei WZ, Philipsen S, Wu GS (2008) Sp1-mediated TRAIL induction in chemosensitization. Cancer Res 68:6718–6726
Zhou L, Ruvolo VR, McQueen T, Chen W, Samudio IJ, Conneely O et al (2013) HDAC inhibition by SNDX-275 (Entinostat) restores expression of silenced leukemia-associated transcription factors Nur77 and Nor1 and of key pro-apoptotic proteins in AML. Leukemia 27:1358–1368
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Ganai, S.A. (2015). HDAC Inhibitors Entinostat and Suberoylanilide Hydroxamic Acid (SAHA): The Ray of Hope for Cancer Therapy. In: Wells, R., Bond, J., Klinman, J., Masters, B., Bell, E. (eds) Molecular Life Sciences. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6436-5_503-1
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DOI: https://doi.org/10.1007/978-1-4614-6436-5_503-1
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