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http://dx.doi.org/10.7314/APJCP.2013.14.12.7095

Selective Inhibition of Bicyclic Tetrapeptide Histone Deacetylase Inhibitor on HDAC4 and K562 Leukemia Cell  

Li, Xiao-Hui (School of Life Science and Biotechnology, Dalian University of Technology)
Huang, Mei-Ling (School of Life Science and Biotechnology, Dalian University of Technology)
Wang, Shi-Miao (School of Life Science and Biotechnology, Dalian University of Technology)
Wang, Qing (School of Pharmaceutical Science and Technology, Dalian University of Technology)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.12, 2013 , pp. 7095-7100 More about this Journal
Abstract
Histone deacetylase (HDAC) inhibitors of cyclic peptide have been proved to be the most complex but the most stable and relative efficient inhibitors because of their large cap region. In this paper, a series of studies were carried out to evaluate the efficacy of synthetic bicyclic tetrapeptide inhibitors 1-5 containing hydroxamic acid referring molecular docking, anti-proliferation, morphology and apoptosis. Docking analysis, together with enzyme inhibitory results, verified the selective capability of inhibitor 4 to HDAC4, which might closely related to haematological tumorigenesis, with Phe227, Asp115, Pro32, His198 and Ser114 participating into hydrophobic interactions and Van der Waals force which was familiar with former study. Moreover, inhibitor 4 inhibited K562 cell line at the $IC_{50}$ value of 1.22 ${\mu}M$ which was 51-67 times more efficient than that for U937 and HL60 cell lines. Inhibitor 4 exhibited the cell cycle-arrested capability to leukemia at S phase or G2/M phase as well as apoptosis-induced ability in different degrees. Finally, we considered that bicyclic tetrapeptide inhibitors were promising inhibitors used in cancer treatment and inhibitor 4 could prevent K562 cell line well from proliferation, arrest cell cycle and induce K562 towards apoptosis to achieve the goals of reversing cancer cells which could become a potential leukemia therapeutic agent in the future.
Keywords
Histone deacetylase inhibitor; bicyclic tetrapeptide; leukemia;
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1 Norikazu N, Yoshikawa D, Watanabe LA, et al (2004). Synthesis and histone deacetylase inhibitory activity of cyclic tetrapeptides containing a retrohydroxamate as zinc ligand. Bioorg Med Chem Lett, 14, 2427-31.   DOI   ScienceOn
2 Rosato RR, Almenara JA, Grant S (2003). The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1. Cancer Res, 63, 3637-45.
3 Singh EK, Ravula S, Pan CM, et al (2008). Synthesis and biological evaluation of histone deacetylase inhibitors that are based on FR235222: A cyclic tetrapeptide scaffold. Bioorg Med Chem Lett, 18, 2549-54.   DOI   ScienceOn
4 Sundstrom C, Nilsson K (1976). Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer, 17, 565-77.   DOI
5 Vega RB, Matsuda K, Oh J, et al (2004). Histone Deacetylase 4 Controls Chondrocyte Hypertrophy during Skeletogenesis. Cell, 119, 555-66.   DOI   ScienceOn
6 Walton JD (2006). HC-toxin. Phytochemistry, 67, 1406-13.   DOI   ScienceOn
7 Wang Y, Wang SY, Zhang XH, et al (2007). FK228 inhibits Hsp90 chaperone function in K562 cells via hyperacetylation of Hsp70. Biochem Bioph Co, 356, 998-1003.   DOI   ScienceOn
8 Ahn MY, Kang DO, Na YJ, et al (2012). Histone deacetylase inhibitor, apicidin, inhibits human ovarian cancer cell migration via class II histone deacetylase 4 silencing. Cancer Lett, 325, 189-99.   DOI   ScienceOn
9 Andersson LC, Nilsson K, Gahmberg CG (1979). K562--A human erythrolekemic cell line. Int J Cancer, 23, 143-7.   DOI
10 Aversanaa CD, Leporeb I, Altucci L (2012). HDAC modulation and cell death in the clinic. Exp Cell Res, 318, 1229-44.   DOI   ScienceOn
11 Bhuiyan MP, Kato T, Okauchi T, et al (2006). Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases. Bioorg Med Chem, 14, 3438-46.   DOI   ScienceOn
12 Byrd JC, Marcucci G, Parthun MR, et al (2005). A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood, 105, 959-67.
13 Collins SJ (1987). The HL-60 Promyelocytic Leukemia Cell Line: Proliferation, Differentiation, and Cellular Oncogene Expression. Blood, 70, 1233-44.
14 Editorial (2009). HDAC inhibitors in leukemia: Current status and perspectives. Leukemia Res, 33, 207-8.   DOI   ScienceOn
15 Fandy TE, Shankar S, Ross DD, Sausville E, Srivastava RK (2005). Interactive effects of HDAC in hibitors and TRAIL on apoptosis are associated with changes in mitochondrial functions and expressions of cell cycle regulatory genes in multiple myeloma. Neoplasia, 7, 646-57.   DOI
16 Furumai R, Matsuyama A, Kobashi N, et al (2002). FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res, 62, 4916-21.
17 Grant C, Rahman F, Piekarz R, et al (2010). Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors. Expert Rev Anticanc, 10, 997-1008.   DOI   ScienceOn
18 Gu WX, Cueto M, Jensen PR, et al (2007). Microsporins A and B: new histone deacetylase inhibitors from the marinederived fungus Microsporum cf. gypseum and the solidphase synthesis of microsporin A. Tetrahedron, 63, 6535-41.   DOI   ScienceOn
19 Goodsell DS, Morris GM, Olson AJ (1996). Automated docking of flexible ligands: applications of AutoDock. J Mol Recognit, 9, 1-5.   DOI   ScienceOn
20 Gottlicher M, Minucci S, Zhu P, et al (2001). Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. Eur Mol Biol Org, 20, 6969-78.   DOI   ScienceOn
21 Grant,S, Chris E; Peter K (2007). Vorinostat. Nat Rev Drug Discov, 6, 21.   DOI   ScienceOn
22 Huang WJ, Chen CC, Chao SW, et al (2011). Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors. Eur J Med Chem, 46, 4042-9.   DOI   ScienceOn
23 Humeniuk R, Mishra PJ, Bertino JR, Banerjee D (2009). Molecular targets for epigenetic therapy of cancer. Curr Pharm Biotechnol, 10, 161-5.   DOI   ScienceOn
24 Im JY, Park H, Kang KW, et al (2008). Modulation of cell cycles and apoptosis by apicidin in estrogen receptor (ER)-positive and -negative human breast cancer cells. Chem Biol Interact, 172, 235-44.   DOI   ScienceOn
25 Islam NM, Kato T, Nishino N, et al (2010). Bicyclic peptides as potent inhibitors of histone deacetylases:Optimization of alkyl loop length. Bioorg Med Chem Lett, 20, 997-9.   DOI   ScienceOn
26 Morris GM, Goodsell DS, Halliday RS, et al (1998). Automated docking using a lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem, 19, 1639-62.   DOI   ScienceOn
27 Josea B, Onikib Y, Kato T, et al (2004). Novel histone deacetylase inhibitors: cyclic tetrapeptide with trifluoromethyl and pentafluoroethyl ketones. Bioorg Med Chen Lett, 14, 5343-6.   DOI   ScienceOn
28 Josea B, Okamura S, Kato T, et al (2004). Toward an HDAC6 inhibitor: synthesis and conformational analysis of cyclic hexapeptide hydroxamic acid designed from $\alpha$-tubulin sequence. Bioorg Med Chem, 12, 1351-6.   DOI   ScienceOn
29 Matsuoka H, Fujimura T, Hayashi M, et al (2007). Disruption of HDAC4/N-CoR complex by histone deacetylase inhibitors leads to inhibition of IL-2 gene expression. Biochem Pharmacol, 74, 465-76.   DOI   ScienceOn
30 Morris GM, Huey R, Lindstrom W, et al (2009). AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility. J Comput Chem, 30, 2785-91.   DOI   ScienceOn
31 Morris GM, Huey R, Olson AJ (2008). Using AutoDock for ligand-receptor docking. Curr Prots in Bioinform, 24, 1-40.
32 Norikazu N, Jose B, Shinta R, et al (2004). Chlamydocin– hydroxamic acid analogues as histone deacetylase inhibitors. Bioorg Med Chem, 12, 5777-84.   DOI   ScienceOn
33 Nishino N, Shivashimpi GM, Soni PB, et al (2008). Interaction of aliphatic cap group in inhibition of histone deacetylases by cyclic tetrapeptides. Bioorg Med Chem, 16, 437-45.   DOI   ScienceOn