Anti-cancer effects of naturally derived compounds targeting histone deacetylase 6-related pathways

Pharmacological Research

Volumn 129, Issue , 2018, Pages 337-356

  Lernoux, Manon ^a   Schnekenburger, Michael ^a   Dicato, Mario ^a   Diederich, Marc ^b  

^a Centre Hospitalier Kirchberg   (Luxembourg)

^b Seoul National University   (South Korea)

Author keywords

Cancer hallmarks; Cancer therapy; HDAC6; HDAC6 inhibitors; Natural compounds

Indexed keywords

ACEROSIDE VIII; ANTINEOPLASTIC AGENT; BUTYRIC ACID; ELLAGIC ACID; EPIGALLOCATECHIN GALLATE; GENISTEIN; GINSENOSIDE; HISTONE DEACETYLASE 6; NATURAL PRODUCTS AND THEIR SYNTHETIC DERIVATIVES; NBM T BBX OS 01; SALIREPOL; SULFORAPHANE; TRICHOSTATIN A; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID; URSOLIC ACID; VANILLIC ACID;

ANTINEOPLASTIC ACTIVITY; CANCER RESISTANCE; CELL MIGRATION; DISEASE ASSOCIATION; DRUG MECHANISM; EPITHELIAL MESENCHYMAL TRANSITION; METASTASIS; NEOVASCULARIZATION (PATHOLOGY); PRIORITY JOURNAL; REVIEW; TUMOR GROWTH; TUMOR INVASION; HUMAN; METABOLISM; NEOPLASM; SIGNAL TRANSDUCTION;

ANTINEOPLASTIC AGENTS; HISTONE DEACETYLASE 6; HUMANS; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 85033793778     PISSN: 10436618     EISSN: 10961186     Source Type: Journal    
DOI: 10.1016/j.phrs.2017.11.004     Document Type: Review

References (238)

1. Hanahanand, D., Weinberg, R.A., Hallmarks of cancer: the next generation. Cell 144 (2011), 646–674.
2. Schnekenburger, M., Florean, C., Dicato, M., Diederich, M., Epigenetic alterations as a universal feature of cancer hallmarks and a promising target for personalized treatments. Curr. Top. Med. Chem. 16 (2016), 745–776.
3. Spange, S., Wagner, T., Heinzel, T., Kramer, O.H., Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Int. J. Biochem. Cell Biol. 41 (2009), 185–198.
4. Choudhary, C., Kumar, C., Gnad, F., Nielsen, M.L., Rehman, M., Walther, T.C., Olsen, J.V., Mann, M., Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325 (2009), 834–840.
5. Wang, Y.C., Peterson, S.E., Loring, J.F., Protein post-translational modifications and regulation of pluripotency in human stem cells. Cell Res. 24 (2014), 143–160.
6. Seidel, C., Schnekenburger, M., Dicato, M., Diederich, M., Antiproliferative and proapoptotic activities of 4-hydroxybenzoic acid-based inhibitors of histone deacetylases. Cancer Lett. 343 (2014), 134–146.
7. Hardyand, T.M., Tollefsbol, T.O., Epigenetic diet: impact on the epigenome and cancer. Epigenomics 3 (2011), 503–518.
8. Vahid, F., Zand, H., Nosrat-Mirshekarlou, E., Najafi, R., Hekmatdoost, A., The role dietary of bioactive compounds on the regulation of histone acetylases and deacetylases: a review. Gene 562 (2015), 8–15.
9. Seidel, C., Schnekenburger, M., Dicato, M., Diederich, M., Histone deacetylase modulators provided by Mother Nature. Genes Nutr. 7 (2012), 357–367.
10. Schnekenburger, M., Dicato, M., Diederich, M., Plant-derived epigenetic modulators for cancer treatment and prevention. Biotechnol. Adv. 32 (2014), 1123–1132.
11. Schnekenburger, M., Dicato, M., Diederich, M., Epigenetic modulators from The Big Blue: a treasure to fight against cancer. Cancer Lett. 351 (2014), 182–197.
12. Seidel, C., Schnekenburger, M., Dicato, M., Diederich, M., Histone deacetylase 6 in health and disease. Epigenomics 7 (2015), 103–118.
13. Batchu, S.N., Brijmohan, A.S., Advani, A., The therapeutic hope for HDAC6 inhibitors in malignancy and chronic disease. Clin. Sci. 130 (2016), 987–1003.
14. Zhang, L., Liu, S., Liu, N., Zhang, Y., Liu, M., Li, D., Seto, E., Yao, T.P., Shui, W., Zhou, J., Proteomic identification and functional characterization of MYH9 Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity. Protein Cell 6 (2015), 42–54.
15. Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X.F., Yao, T.P., HDAC6 is a microtubule-associated deacetylase. Nature 417 (2002), 455–458.
16. Bertos, N.R., Gilquin, B., Chan, G.K., Yen, T.J., Khochbin, S., Yang, X.J., Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention. J. Biol. Chem. 279 (2004), 48246–48254.
17. Seigneurin-Berny, D., Verdel, A., Curtet, S., Lemercier, C., Garin, J., Rousseaux, S., Khochbin, S., Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways. Mol. Cell. Biol. 21 (2001), 8035–8044.
18. Pai, M.T., Tzeng, S.R., Kovacs, J.J., Keaton, M.A., Li, S.S., Yao, T.P., Zhou, P., Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin. J. Mol. Biol. 370 (2007), 290–302.
19. Li, Y., Shin, D., Kwon, S.H., Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes. FEBS J. 280 (2013), 775–793.
20. Haggarty, S.J., Koeller, K.M., Wong, J.C., Grozinger, C.M., Schreiber, S.L., Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc. Natl. Acad. Sci. U. S. A. 100 (2003), 4389–4394.
21. Zou, H., Wu, Y., Navre, M., Sang, B.C., Characterization of the two catalytic domains in histone deacetylase 6. Biochem. Biophys. Res. Commun. 341 (2006), 45–50.
22. Haiand, Y., Christianson, D.W., Histone deacetylase 6 structure and molecular basis of catalysis and inhibition. Nat. Chem. Biol. 12 (2016), 741–747.
23. Liu, Y., Li, L., Min, J., Structural biology: HDAC6 finally crystal clear. Nat. Chem. Biol. 12 (2016), 660–661.
24. Miyake, Y., Keusch, J.J., Wang, L., Saito, M., Hess, D., Wang, X., Melancon, B.J., Helquist, P., Gut, H., Matthias, P., Structural insights into HDAC6 tubulin deacetylation and its selective inhibition. Nat. Chem. Biol. 12 (2016), 748–754.
25. Kramer, O.H., Mahboobi, S., Sellmer, A., Drugging the HDAC6-HSP90 interplay in malignant cells. Trends Pharmacol. Sci. 35 (2014), 501–509.
26. Di Fulvio, S., Azakir, B.A., Therrien, C., Sinnreich, M., Dysferlin interacts with histone deacetylase 6 and increases alpha-tubulin acetylation. PLoS One, 6, 2011, e28563.
27. Wu, Y., Song, S.W., Sun, J., Bruner, J.M., Fuller, G.N., Zhang, W., IIp45 inhibits cell migration through inhibition of HDAC6. J. Biol. Chem. 285 (2010), 3554–3560.
28. Tokesi, N., Lehotzky, A., Horvath, I., Szabo, B., Olah, J., Lau, P., Ovadi, J., TPPP/p25 promotes tubulin acetylation by inhibiting histone deacetylase 6. J. Biol. Chem. 285 (2010), 17896–17906.
29. Zhou, J., Vos, C.C., Gjyrezi, A., Yoshida, M., Khuri, F.R., Tamanoi, F., Giannakakou, P., The protein farnesyltransferase regulates HDAC6 activity in a microtubule-dependent manner. J. Biol. Chem. 284 (2009), 9648–9655.
30. Aldana-Masangkayand, G.I., Sakamoto, K.M., The role of HDAC6 in cancer. J. Biomed. Biotechnol., 2011, 2011, 875824.
31. Zheng, K., Jiang, Y., He, Z., Kitazato, K., Wang, Y., Cellular defence or viral assist: the dilemma of HDAC6. J. Gen. Virol. 98 (2017), 322–337.
32. Kalin, J.H., Butler, K.V., Akimova, T., Hancock, W.W., Kozikowski, A.P., Second-generation histone deacetylase 6 inhibitors enhance the immunosuppressive effects of Foxp3+ T-regulatory cells. J. Med. Chem. 55 (2012), 639–651.
33. Lee, Y.S., Lim, K.H., Guo, X., Kawaguchi, Y., Gao, Y., Barrientos, T., Ordentlich, P., Wang, X.F., Counter, C.M., Yao, T.P., The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis. Cancer Res. 68 (2008), 7561–7569.
34. Yang, P.H., Zhang, L., Zhang, Y.J., Zhang, J., Xu, W.F., HDAC6: physiological function and its selective inhibitors for cancer treatment. Drug Discov. Ther. 7 (2013), 233–242.
35. de Ruijter, A.J., van Gennip, A.H., Caron, H.N., Kemp, S., van Kuilenburg, A.B., Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem. J. 370 (2003), 737–749.
36. Bruningand, A., Juckstock, J., Misfolded proteins: from little villains to little helpers in the fight against cancer. Front. Oncol., 5, 2015, 47.
37. Wickstrom, S.A., Masoumi, K.C., Khochbin, S., Fassler, R., Massoumi, R., CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin. EMBO J. 29 (2010), 131–144.
38. Chuang, M.J., Wu, S.T., Tang, S.H., Lai, X.M., Lai, H.C., Hsu, K.H., Sun, K.H., Sun, G.H., Chang, S.Y., Yu, D.S., Hsiao, P.W., Huang, S.M., Cha, T.L., The HDAC inhibitor LBH589 induces ERK-dependent prometaphase arrest in prostate cancer via HDAC6 inactivation and down-regulation. PLoS One, 8, 2013, e73401.
39. Nogues, L., Reglero, C., Rivas, V., Salcedo, A., Lafarga, V., Neves, M., Ramos, P., Mendiola, M., Berjon, A., Stamatakis, K., Zhou, X.Z., Lu, K.P., Hardisson, D., Mayor, F. Jr., Penela, P., G protein-coupled receptor kinase 2 (GRK2) promotes Breast tumorigenesis through a HDAC6-Pin1 axis. EBioMedicine 13 (2016), 132–145.
40. Li, S., Liu, X., Chen, X., Zhang, L., Wang, X., Histone deacetylase 6 promotes growth of glioblastoma through inhibition of SMAD2 signaling. Tumour Biol. 36 (2015), 9661–9665.
41. Ding, G., Liu, H.D., Huang, Q., Liang, H.X., Ding, Z.H., Liao, Z.J., Huang, G., HDAC6 promotes hepatocellular carcinoma progression by inhibiting P53 transcriptional activity. FEBS Lett. 587 (2013), 880–886.
42. Kaluza, D., Kroll, J., Gesierich, S., Yao, T.P., Boon, R.A., Hergenreider, E., Tjwa, M., Rossig, L., Seto, E., Augustin, H.G., Zeiher, A.M., Dimmeler, S., Urbich, C., Class IIb HDAC6 regulates endothelial cell migration and angiogenesis by deacetylation of cortactin. EMBO J. 30 (2011), 4142–4156.
43. Ryu, H.W., Won, H.R., Lee, D.H., Kwon, S.H., HDAC6 regulates sensitivity to cell death in response to stress and post-stress recovery. Cell Stress Chaperones 22 (2017), 253–261.
44. Qian, D.Z., Kachhap, S.K., Collis, S.J., Verheul, H.M., Carducci, M.A., Atadja, P., Pili, R., Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res. 66 (2006), 8814–8821.
45. Park, J.H., Kim, S.H., Choi, M.C., Lee, J., Oh, D.Y., Im, S.A., Bang, Y.J., Kim, T.Y., Class II histone deacetylases play pivotal roles in heat shock protein 90-mediated proteasomal degradation of vascular endothelial growth factor receptors. Biochem. Biophys. Res. Commun. 368 (2008), 318–322.
46. Li, D., Xie, S., Ren, Y., Huo, L., Gao, J., Cui, D., Liu, M., Zhou, J., Microtubule-associated deacetylase HDAC6 promotes angiogenesis by regulating cell migration in an EB1-dependent manner. Protein Cell 2 (2011), 150–160.
47. Lv, Z., Weng, X., Du, C., Zhang, C., Xiao, H., Cai, X., Ye, S., Cheng, J., Ding, C., Xie, H., Zhou, L., Wu, J., Zheng, S., Downregulation of HDAC6 promotes angiogenesis in hepatocellular carcinoma cells and predicts poor prognosis in liver transplantation patients. Mol. Carcinog. 55 (2016), 1024–1033.
48. Kalinand, J.H., Bergman, J.A., Development and therapeutic implications of selective histone deacetylase 6 inhibitors. J. Med. Chem. 56 (2013), 6297–6313.
49. Gu, S., Liu, Y., Zhu, B., Ding, K., Yao, T.P., Chen, F., Zhan, L., Xu, P., Ehrlich, M., Liang, T., Lin, X., Feng, X.H., Loss of alpha-tubulin acetylation is associated with TGF-beta-induced epithelial-Mesenchymal transition. J. Biol. Chem. 291 (2016), 5396–5405.
50. Deskin, B., Lasky, J., Zhuang, Y., Shan, B., Requirement of HDAC6 for activation of Notch1 by TGF-beta1. Sci. Rep., 6, 2016, 31086.
51. Shan, B., Yao, T.P., Nguyen, H.T., Zhuo, Y., Levy, D.R., Klingsberg, R.C., Tao, H., Palmer, M.L., Holder, K.N., Lasky, J.A., Requirement of HDAC6 for transforming growth factor-beta1-induced epithelial-mesenchymal transition. J. Biol. Chem. 283 (2008), 21065–21073.
52. Boyault, C., Sadoul, K., Pabion, M., Khochbin, S., HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination. Oncogene 26 (2007), 5468–5476.
53. Saji, S., Kawakami, M., Hayashi, S., Yoshida, N., Hirose, M., Horiguchi, S., Itoh, A., Funata, N., Schreiber, S.L., Yoshida, M., Toi, M., Significance of HDAC6 regulation via estrogen signaling for cell motility and prognosis in estrogen receptor-positive breast cancer. Oncogene 24 (2005), 4531–4539.
54. Hou, H., Zhao, L., Chen, W., Li, J., Zuo, Q., Zhang, G., Zhang, X., Li, X., Expression and significance of cortactin and HDAC6 in human prostatic foamy gland carcinoma. Int. J. Exp. Pathol. 96 (2015), 248–254.
55. Ding, N., Ping, L., Feng, L., Zheng, X., Song, Y., Zhu, J., Histone deacetylase 6 activity is critical for the metastasis of Burkitt's lymphoma cells. Cancer Cell Int., 14, 2014, 139.
56. Zhang, L., Liu, N., Xie, S., He, X., Zhou, J., Liu, M., Li, D., HDAC6 regulates neuroblastoma cell migration and may play a role in the invasion process. Cancer. Biol. Ther. 15 (2014), 1561–1570.
57. Kanno, K., Kanno, S., Nitta, H., Uesugi, N., Sugai, T., Masuda, T., Wakabayashi, G., Maesawa, C., Overexpression of histone deacetylase 6 contributes to accelerated migration and invasion activity of hepatocellular carcinoma cells. Oncol. Rep. 28 (2012), 867–873.
58. Zuo, Q., Wu, W., Li, X., Zhao, L., Chen, W., HDAC6 and SIRT2 promote bladder cancer cell migration and invasion by targeting cortactin. Oncol. Rep. 27 (2012), 819–824.
59. Li, D., Sun, X., Zhang, L., Yan, B., Xie, S., Liu, R., Liu, M., Zhou, J., Histone deacetylase 6 and cytoplasmic linker protein 170 function together to regulate the motility of pancreatic cancer cells. Protein Cell 5 (2014), 214–223.
60. Liu, J., Gu, J., Feng, Z., Yang, Y., Zhu, N., Lu, W., Qi, F., Both HDAC5 and HDAC6 are required for the proliferation and metastasis of melanoma cells. J. Transl. Med., 14(7), 2016, C6.
61. Azuma, K., Urano, T., Horie-Inoue, K., Hayashi, S., Sakai, R., Ouchi, Y., Inoue, S., Association of estrogen receptor alpha and histone deacetylase 6 causes rapid deacetylation of tubulin in breast cancer cells. Cancer Res. 69 (2009), 2935–2940.
62. Limand, J.A., Juhnn, Y.S., Isoproterenol increases histone deacetylase 6 expression and cell migration by inhibiting ERK signaling via PKA and Epac pathways in human lung cancer cells. Exp. Mol. Med., 48, 2016, e204.
63. Wang, Z., Tang, F., Hu, P., Wang, Y., Gong, J., Sun, S., Xie, C., HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma. Oncol. Rep. 36 (2016), 589–597.
64. Wang, Z., Hu, P., Tang, F., Xie, C., HDAC6-mediated EGFR stabilization and activation restrict cell response to sorafenib in non-small cell lung cancer cells. Med. Oncol., 33, 2016, 50.
65. Li, Z.Y., Zhang, C., Zhang, Y., Chen, L., Chen, B.D., Li, Q.Z., Zhang, X.J., Li, W.P., A novel HDAC6 inhibitor tubastatin A: controls HDAC6-p97/VCP-mediated ubiquitination-autophagy turnover and reverses temozolomide-induced ER stress-tolerance in GBM cells. Cancer Lett. 391 (2017), 89–99.
66. Lee, J.H., Mahendran, A., Yao, Y., Ngo, L., Venta-Perez, G., Choy, M.L., Kim, N., Ham, W.S., Breslow, R., Marks, P.A., Development of a histone deacetylase 6 inhibitor and its biological effects. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 15704–15709.
67. Namdar, M., Perez, G., Ngo, L., Marks, P.A., Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 20003–20008.
68. Marcus, A.I., Zhou, J., O'Brate, A., Hamel, E., Wong, J., Nivens, M., El-Naggar, A., Yao, T.P., Khuri, F.R., Giannakakou, P., The synergistic combination of the farnesyl transferase inhibitor lonafarnib and paclitaxel enhances tubulin acetylation and requires a functional tubulin deacetylase. Cancer Res. 65 (2005), 3883–3893.
69. Wang, L., Xiang, S., Williams, K.A., Dong, H., Bai, W., Nicosia, S.V., Khochbin, S., Bepler, G., Zhang, X., Depletion of HDAC6 enhances cisplatin-induced DNA damage and apoptosis in non-small cell lung cancer cells. PLoS One, 7, 2012, e44265.
70. Aldana-Masangkay, G.I., Rodriguez-Gonzalez, A., Lin, T., Ikeda, A.K., Hsieh, Y.T., Kim, Y.M., Lomenick, B., Okemoto, K., Landaw, E.M., Wang, D., Mazitschek, R., Bradner, J.E., Sakamoto, K.M., Tubacin suppresses proliferation and induces apoptosis of acute lymphoblastic leukemia cells. Leukemia Lymphoma 52 (2011), 1544–1555.
71. Florean, C., Schnekenburger, M., Grandjenette, C., Dicato, M., Diederich, M., Epigenomics of leukemia: from mechanisms to therapeutic applications. Epigenomics 3 (2011), 581–609.
72. Losson, H., Schnekenburger, M., Dicato, M., Diederich, M., Natural compound histone deacetylase inhibitors (HDACi): synergy with inflammatory signaling pathway modulators and clinical applications in cancer. Molecules, 21, 2016.
73. Schnekenburger, M., Morceau, F., Henry, E., Blasius, R., Dicato, M., Trentesaux, C., Diederich, M., Transcriptional and post-transcriptional regulation of glutathione S-transferase P1 expression during butyric acid-induced differentiation of K562 cells. Leuk. Res. 30 (2006), 561–568.
74. Kumagai, T., Wakimoto, N., Yin, D., Gery, S., Kawamata, N., Takai, N., Komatsu, N., Chumakov, A., Imai, Y., Koeffler, H.P., Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (Vorinostat, SAHA) profoundly inhibits the growth of human pancreatic cancer cells. Int. J. Cancer 121 (2007), 656–665.
75. Bhatnagar, N., Li, X., Chen, Y., Zhou, X., Garrett, S.H., Guo, B., 3,3’-diindolylmethane enhances the efficacy of butyrate in colon cancer prevention through down-regulation of survivin. Cancer Prev. Res. 2 (2009), 581–589.
76. Xargay-Torrent, S., Lopez-Guerra, M., Saborit-Villarroya, I., Rosich, L., Campo, E., Roue, G., Colomer, D., Vorinostat-induced apoptosis in mantle cell lymphoma is mediated by acetylation of proapoptotic BH3-only gene promoters. Clin. Cancer Res. 17 (2011), 3956–3968.
77. Seidel, C., Florean, C., Schnekenburger, M., Dicato, M., Diederich, M., Chromatin-modifying agents in anti-cancer therapy. Biochimie 94 (2012), 2264–2279.
78. Balasubramanian, S., Verner, E., Buggy, J.J., Isoform-specific histone deacetylase inhibitors: the next step?. Cancer Lett. 280 (2009), 211–221.
79. Butler, K.V., Kalin, J., Brochier, C., Vistoli, G., Langley, B., Kozikowski, A.P., Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J. Am. Chem. Soc. 132 (2010), 10842–10846.
80. Vogl, D.T., Raje, N., Jagannath, S., Richardson, P., Hari, P., Orlowski, R., Supko, J.G., Tamang, D., Yang, M., Jones, S.S., Wheeler, C., Markelewicz, R.J., Lonial, S., Ricolinostat, the first selective histone deacetylase 6 inhibitor, in combination with bortezomib and dexamethasone for relapsed or refractory multiple myeloma. Clin. Cancer Res. 23 (2017), 3307–3315.
81. Huang, Z., Huang, Q., Ji, L., Wang, Y., Qi, X., Liu, L., Liu, Z., Lu, L., Epigenetic regulation of active Chinese herbal components for cancer prevention and treatment: a follow-up review. Pharmacol. Res. 114 (2016), 1–12.
82. Rashidi, B., Malekzadeh, M., Goodarzi, M., Masoudifar, A., Mirzaei, H., Green tea and its anti-angiogenesis effects. Biomed. Pharmacother.=Biomed. Pharmacother. 89 (2017), 949–956.
83. Shirakami, Y., Shimizu, M., Moriwaki, H., Cancer chemoprevention with green tea catechins: from bench to bed. Curr. Drug Targets 13 (2012), 1842–1857.
84. Gan, R.Y., Li, H.B., Sui, Z.Q., Corke, H., Absorption, metabolism, anti-Cancer effect and molecular targets of epigallocatechin gallate (EGCG): an updated review. Crit. Rev. Food Sci Nutr., 2016, 1–18.
85. Yangand, C.S., Wang, H., Cancer preventive activities of tea catechins. Molecules, 21, 2016.
86. Shankar, S., Suthakar, G., Srivastava, R.K., Epigallocatechin-3-gallate inhibits cell cycle and induces apoptosis in pancreatic cancer. Front. Biosci. 12 (2007), 5039–5051.
87. Shirakami, Y., Shimizu, M., Adachi, S., Sakai, H., Nakagawa, T., Yasuda, Y., Tsurumi, H., Hara, Y., Moriwaki, H., (−)-Epigallocatechin gallate suppresses the growth of human hepatocellular carcinoma cells by inhibiting activation of the vascular endothelial growth factor-vascular endothelial growth factor receptor axis. Cancer Sci. 100 (2009), 1957–1962.
88. Zhang, Q., Tang, X., Lu, Q., Zhang, Z., Rao, J., Le, A.D., Green tea extract and (−)-epigallocatechin-3-gallate inhibit hypoxia- and serum-induced HIF-1alpha protein accumulation and VEGF expression in human cervical carcinoma and hepatoma cells. Mol. Cancer Ther. 5 (2006), 1227–1238.
89. Thakur, V.S., Gupta, K., Gupta, S., Green tea polyphenols causes cell cycle arrest and apoptosis in prostate cancer cells by suppressing class I histone deacetylases. Carcinogenesis 33 (2012), 377–384.
90. Fujiki, H., Sueoka, E., Watanabe, T., Suganuma, M., Synergistic enhancement of anticancer effects on numerous human cancer cell lines treated with the combination of EGCG, other green tea catechins, and anticancer compounds. J. Cancer Res. Clin. Oncol. 141 (2015), 1511–1522.
91. Oya, Y., Mondal, A., Rawangkan, A., Umsumarng, S., Iida, K., Watanabe, T., Kanno, M., Suzuki, K., Li, Z., Kagechika, H., Shudo, K., Fujiki, H., Suganuma, M., Down-regulation of histone deacetylase 4, −5 and −6 as a mechanism of synergistic enhancement of apoptosis in human lung cancer cells treated with the combination of a synthetic retinoid, Am80 and green tea catechin. J. Nutr. Biochem. 42 (2017), 7–16.
92. Ju, E.M., Lee, S.E., Hwang, H.J., Kim Antioxidant and, J.H., anticancer activity of extract from Betula platyphylla var. japonica. Life Sci. 74 (2004), 1013–1026.
93. Rastogi, S., Pandey, M.M., Kumar Singh Rawat, A., Medicinal plants of the genus Betula–traditional uses and a phytochemical-pharmacological review. J. Ethnopharmacol. 159 (2015), 62–83.
94. Lee, M., Park, J.H., Min, D.S., Yoo, H., Park, J.H., Kim, Y.C., Sung, S.H., Antifibrotic activity of diarylheptanoids from Betula platyphylla toward HSC-T6 cells. Biosci. Biotechnol. Biochem. 76 (2012), 1616–1620.
95. Ryu, H.W., Lee, D.H., Shin, D.H., Kim, S.H., Kwon, S.H., Aceroside VIII is a new natural selective HDAC6 inhibitor that synergistically enhances the anticancer activity of HDAC inhibitor in HT29 cells. Planta Med. 81 (2015), 222–227.
96. Lederand, A., Leder, P., Butyric acid: a potent inducer of erythroid differentiation in cultured erythroleukemic cells. Cell 5 (1975), 319–322.
97. Sealyand, L., Chalkley, R., The effect of sodium butyrate on histone modification. Cell 14 (1978), 115–121.
98. Myzakand, M.C., Dashwood, R.H., Histone deacetylases as targets for dietary cancer preventive agents: lessons learned with butyrate, diallyl disulfide, and sulforaphane. Curr. Drug Targets 7 (2006), 443–452.
99. Scharlau, D., Borowicki, A., Habermann, N., Hofmann, T., Klenow, S., Miene, C., Munjal, U., Stein, K., Glei, M., Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat. Res. 682 (2009), 39–53.
100. Edmond, V., Brambilla, C., Brambilla, E., Gazzeri, S., Eymin, B., SRSF2 is required for sodium butyrate-mediated p21(WAF1) induction and premature senescence in human lung carcinoma cell lines. ABBV Cell Cycle 10 (2011), 1968–1977.
101. Alberto, R.R., Yudibeth, S.L., Jonathan, F.M., Raul, F.M., Cristina, C.L., Ismael, V.M., Cecilia, R.M., Martiniano, B., Martinez-Archundia, M., Guadalupe, T.J., Elvia, B.M., Jose, C.B., Design, synthesis and biological evaluation of a phenyl butyric acid derivative, N-(4-chlorophenyl)-4-phenylbutanamide: a HDAC6 inhibitor with anti-proliferative activity on cervix cancer and leukemia cells. Anticancer Agents Med. Chem. 17 (2017), 1441–1454.
102. Tejada, S., Manayi, A., Daglia, M., Nabavi, S.F., Sureda, A., Hajheydari, Z., Gortzi, O., Pazoki-Toroudi, H., Nabavi, S.M., Wound Healing Effects of Curcumin: A Short Review. Curr. Pharm. Biotechnol. 17 (2016), 1002–1007.
103. Shehzad, A., Wahid, F., Lee, Y.S., Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch. Pharm. 343 (2010), 489–499.
104. Duvoix, A., Blasius, R., Delhalle, S., Schnekenburger, M., Morceau, F., Henry, E., Dicato, M., Diederich, M., Chemopreventive and therapeutic effects of curcumin. Cancer Lett. 223 (2005), 181–190.
105. Teiten, M.H., Dicato, M., Diederich, M., Curcumin as a regulator of epigenetic events. Mol. Nutr. Food Res. 57 (2013), 1619–1629.
106. Liu, H.L., Chen, Y., Cui, G.H., Zhou, J.F., Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation. Acta Pharmacol. Sin. 26 (2005), 603–609.
107. Wang, S.H., Lin, P.Y., Chiu, Y.C., Huang, J.S., Kuo, Y.T., Wu, J.C., Chen, C.C., Curcumin-Mediated HDAC inhibition suppresses the DNA damage response and contributes to increased DNA damage sensitivity. PLoS One, 10, 2015, e0134110.
108. Guo, Y., Shu, L., Zhang, C., Su, Z.Y., Kong, A.N., Curcumin inhibits anchorage-independent growth of HT29 human colon cancer cells by targeting epigenetic restoration of the tumor suppressor gene DLEC1. Biochem. Pharmacol. 94 (2015), 69–78.
109. Huang, H.C., Tang, D., Xu, K., Jiang, Z.F., Curcumin attenuates amyloid-beta-induced tau hyperphosphorylation in human neuroblastoma SH-SY5Y cells involving PTEN/Akt/GSK-3beta signaling pathway. J. Recept. Signal Transduct. Res. 34 (2014), 26–37.
110. Sarkar, R., Mukherjee, A., Mukherjee, S., Biswas, R., Biswas, J., Roy, M., Curcumin augments the efficacy of antitumor drugs used in leukemia by modulation of heat shock proteins via HDAC6. J. Environ. Pathol. Toxicol. Oncol. 33 (2014), 247–263.
111. Vlachojannis, C., Zimmermann, B.F., Chrubasik-Hausmann, S., Efficacy and safety of pomegranate medicinal products for cancer. Evid.-based Complem. Altern. Med.: eCAM, 2015, 2015, 258598.
112. Ceci, C., Tentori, L., Atzori, M.G., Lacal, P.M., Bonanno, E., Scimeca, M., Cicconi, R., Mattei, M., de Martino, M.G., Vespasiani, G., Miano, R., Graziani, G., Ellagic acid inhibits bladder cancer invasiveness and In vivo tumor growth. Nutrients, 8, 2016.
113. Zhang, H.M., Zhao, L., Li, H., Xu, H., Chen, W.W., Tao, L., Research progress on the anticarcinogenic actions and mechanisms of ellagic acid. Cancer Biol. Med. 11 (2014), 92–100.
114. Kowshik, J., Giri, H., Kishore, T.K., Kesavan, R., Vankudavath, R.N., Reddy, G.B., Dixit, M., Nagini, S., Ellagic acid inhibits VEGF/VEGFR2, PI3K/Akt and MAPK signaling cascades in the hamster cheek pouch carcinogenesis model. Anticancer Agents Med. Chem. 14 (2014), 1249–1260.
115. Banerjee, S., Li, Y., Wang, Z., Sarkar, F.H., Multi-targeted therapy of cancer by genistein. Cancer Lett. 269 (2008), 226–242.
116. Rietjens, I.M., Sotoca, A.M., Vervoort, J., Louisse, J., Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks. Mol. Nutr. Food Res. 57 (2013), 100–113.
117. Russo, M., Russo, G.L., Daglia, M., Kasi, P.D., Ravi, S., Nabavi, S.F., Nabavi, S.M., Understanding genistein in cancer: the good and the bad effects: a review. Food Chem. 196 (2016), 589–600.
118. Ganaiand, A.A., Farooqi, H., Bioactivity of genistein: a review of in vitro and in vivo studies. Biomed. Pharmacother.=Biomed. Pharmacother. 76 (2015), 30–38.
119. Basak, S., Pookot, D., Noonan, E.J., Dahiya, R., Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function. Mol. Cancer Ther. 7 (2008), 3195–3202.
120. Lu, J.M., Yao, Q., Chen, C., Ginseng compounds: an update on their molecular mechanisms and medical applications. Curr. Vasc. Pharmacol. 7 (2009), 293–302.
121. Liu, Z.H., Li, J., Xia, J., Jiang, R., Zuo, G.W., Li, X.P., Chen, Y., Xiong, W., Chen, D.L., Ginsenoside 20(s)-Rh2 as potent natural histone deacetylase inhibitors suppressing the growth of human leukemia cells. Chem. Biol. Interact. 242 (2015), 227–234.
122. Shi, Q., Shi, X., Zuo, G., Xiong, W., Li, H., Guo, P., Wang, F., Chen, Y., Li, J., Chen, D.L., Anticancer effect of 20(S)-ginsenoside Rh2 on HepG2 liver carcinoma cells: activating GSK-3beta and degrading beta-catenin. Oncol. Rep. 36 (2016), 2059–2070.
123. Han, S., Jeong, A.J., Yang, H., Bin Kang, K., Lee, H., Yi, E.H., Kim, B.H., Cho, C.H., Chung, J.W., Sung, S.H., Ye, S.K., Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through targeting IL-6-induced JAK2/STAT3 pathway in human colorectal cancer cells. J. Ethnopharmacol. 194 (2016), 83–90.
124. Shi, Q., Li, J., Feng, Z., Zhao, L., Luo, L., You, Z., Li, D., Xia, J., Zuo, G., Chen, D., Effect of ginsenoside Rh2 on the migratory ability of HepG2 liver carcinoma cells: recruiting histone deacetylase and inhibiting activator protein 1 transcription factors. Mol. Med. Rep. 10 (2014), 1779–1785.
125. Zhang, Z.R., Leung, W.N., Cheung, H.Y., Chan, C.W., Osthole a review on its bioactivities, pharmacological properties, and potential as alternative medicine. Evid.-based Complem. Altern. Med.: eCAM, 2015, 2015, 919616.
126. Yang, H.Y., Hsu, Y.F., Chiu, P.T., Ho, S.J., Wang, C.H., Chi, C.C., Huang, Y.H., Lee, C.F., Li, Y.S., Ou, G., Hsu, M.J., Anti-cancer activity of an osthole derivative, NBM-T-BMX-O: targeting vascular endothelial growth factor receptor signaling and angiogenesis. PLoS One, 8, 2013, e81592.
127. Huang, W.J., Chen, C.C., Chao, S.W., Lee, S.S., Hsu, F.L., Lu, Y.L., Hung, M.F., Chang, C.I., Synthesis of N-hydroxycinnamides capped with a naturally occurring moiety as inhibitors of histone deacetylase. ChemMedChem 5 (2010), 598–607.
128. Huang, W.J., Chen, C.C., Chao, S.W., Yu, C.C., Yang, C.Y., Guh, J.H., Lin, Y.C., Kuo, C.I., Yang, P., Chang, C.I., Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors. Eur. J. Med. Chem. 46 (2011), 4042–4049.
129. Pai, J.T., Hsu, C.Y., Hua, K.T., Yu, S.Y., Huang, C.Y., Chen, C.N., Liao, C.H., Weng, M.S., NBM-T-BBX-OS01, semisynthesized from osthole, induced G1 growth arrest through HDAC6 inhibition in lung cancer cells. Molecules 20 (2015), 8000–8019.
130. Li, Y., Li, X., Son, B.W., Antibacterial and radical scavenging epoxycyclohexenones and aromatic polyols from a marine isolate of the fungus Aspergillus. Nat. Prod. Sci. 11 (2005), 136–138.
131. Ali, T., Inagaki, M., Chai, H.B., Wieboldt, T., Rapplye, C., Rakotondraibe, L.H., Halogenated compounds from directed fermentation of penicillium concentricum, an endophytic fungus of the liverwort trichocolea tomentella. J. Nat. Prod. 80 (2017), 1397–1403.
132. Zwick, V., Allard, P.M., Ory, L., Simoes-Pires, C.A., Marcourt, L., Gindro, K., Wolfender, J.L., Cuendet, M., UHPLC-MS-based HDAC assay applied to bio-guided microfractionation of fungal extracts. Phytochem. Anal.: PCA 28 (2017), 93–100.
133. Zhang, Y., Talalay, P., Cho, C.G., Posner, G.H., A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc. Natl. Acad. Sci. U. S. A. 89 (1992), 2399–2403.
134. Russo, M., Spagnuolo, C., Russo, G.L., Skalicka-Wozniak, K., Daglia, M., Sobarzo-Sanchez, E., Nabavi, S.F., Nabavi, S.M., Nrf2 targeting by sulforaphane: a potential therapy for cancer treatment. Crit. Rev. Food Sci. Nutr., 2016, 1–15.
135. Clarke, J.D., Dashwood, R.H., Ho, E., Multi-targeted prevention of cancer by sulforaphane. Cancer Lett. 269 (2008), 291–304.
136. Leone, A., Diorio, G., Sexton, W., Schell, M., Alexandrow, M., Fahey, J.W., Kumar, N.B., Sulforaphane for the chemoprevention of bladder cancer: molecular mechanism targeted approach. Oncotarget 8 (2017), 35412–35424.
137. Ganai, S.A., Rashid, R., Abdullah, E., Altaf, M., Plant derived inhibitor Sulforaphane in combinatorial therapy against therapeutically challenging Pancreatic Cancer. Anticancer Agents Med. Chem. 17 (2016), 365–373.
138. Ganai, S.A., Histone deacetylase inhibitor sulforaphane: the phytochemical with vibrant activity against prostate cancer. Biomed. Pharmacother.=Biomed. Pharmacother. 81 (2016), 250–257.
139. Holmstrom, K.M., Kostov, R.V., Dinkova-Kostova, A.T., The multifaceted role of Nrf2 in mitochondrial function. Curr. Opin. Toxicol. 1 (2016), 80–91.
140. Dickinson, S.E., Rusche, J.J., Bec, S.L., Horn, D.J., Janda, J., Rim, S.H., Smith, C.L., Bowden, G.T., The effect of sulforaphane on histone deacetylase activity in keratinocytes: differences between in vitro and in vivo analyses. Mol. Carcinog. 54 (2015), 1513–1520.
141. Myzak, M.C., Karplus, P.A., Chung, F.L., Dashwood, R.H., A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. Cancer Res. 64 (2004), 5767–5774.
142. Rajendran, P., Kidane, A.I., Yu, T.W., Dashwood, W.M., Bisson, W.H., Lohr, C.V., Ho, E., Williams, D.E., Dashwood, R.H., HDAC turnover: ctIP acetylation and dysregulated DNA damage signaling in colon cancer cells treated with sulforaphane and related dietary isothiocyanates. Epigenetics 8 (2013), 612–623.
143. Gaoand, L., Alumkal, J., Epigenetic regulation of androgen receptor signaling in prostate cancer. Epigenetics 5 (2010), 100–104.
144. Gibbs, A., Schwartzman, J., Deng, V., Alumkal, J., Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6. Proc. Natl. Acad. Sci. U. S. A. 106 (2009), 16663–16668.
145. Clarke, J.D., Hsu, A., Yu, Z., Dashwood, R.H., Ho, E., Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol. Nutr. Food Res. 55 (2011), 999–1009.
146. Tsuji, N., Kobayashi, M., Nagashima, K., Wakisaka, Y., Koizumi, K., A new antifungal antibiotic: trichostatin. J. Antibiotics 29 (1976), 1–6.
147. Yoshida, M., Kijima, M., Akita, M., Beppu, T., Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J. Biol. Chem. 265 (1990), 17174–17179.
148. Dickinson, M., Johnstone, R.W., Prince, H.M., Histone deacetylase inhibitors: potential targets responsible for their anti-cancer effect. Invest. New Drugs 28:Suppl 1 (2010), S3–S20.
149. Medler, T.R., Craig, J.M., Fiorillo, A.A., Feeney, Y.B., Harrell, J.C., Clevenger, C.V., HDAC6 deacetylates HMGN2 to regulate stat5a activity and Breast cancer growth. Mol. Cancer Res.: MCR 14 (2016), 994–1008.
150. Meng, Z., Jia, L.F., Gan, Y.H., PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition. Oncogene 35 (2016), 2333–2344.
151. Li, L., Fang, R., Liu, B., Shi, H., Wang, Y., Zhang, W., Zhang, X., Ye, L., Deacetylation of tumor-suppressor MST1 in Hippo pathway induces its degradation through HBXIP-elevated HDAC6 in promotion of breast cancer growth. Oncogene 35 (2016), 4048–4057.
152. Changand, I., Wang, C.Y., Inhibition of HDAC6 protein enhances bortezomib-induced apoptosis in head and neck squamous cell carcinoma (HNSCC) by reducing autophagy. J. Biol. Chem. 291 (2016), 18199–18209.
153. Matsuyama, A., Shimazu, T., Sumida, Y., Saito, A., Yoshimatsu, Y., Seigneurin-Berny, D., Osada, H., Komatsu, Y., Nishino, N., Khochbin, S., Horinouchi, S., Yoshida, M., In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. EMBO J. 21 (2002), 6820–6831.
154. Zhu, Q.Y., Wang, Z., Ji, C., Cheng, L., Yang, Y.L., Ren, J., Jin, Y.H., Wang, Q.J., Gu, X.J., Bi, Z.G., Hu, G., Yang, Y., C6-ceramide synergistically potentiates the anti-tumor effects of histone deacetylase inhibitors via AKT dephosphorylation and alpha-tubulin hyperacetylation both in vitro and in vivo. Cell. Death. Dis., 2, 2011, e117.
155. Odermatt, A., Da Cunha, T., Penno, C.A., Chandsawangbhuwana, C., Reichert, C., Wolf, A., Dong, M., Baker, M.E., Hepatic reduction of the secondary bile acid 7-oxolithocholic acid is mediated by 11beta-hydroxysteroid dehydrogenase 1. Biochem. J. 436 (2011), 621–629.
156. Saffioti, F., Gurusamy, K.S., Hawkins, N., Toon, C.D., Tsochatzis, E., Davidson, B.R., Thorburn, D., Pharmacological interventions for primary sclerosing cholangitis: an attempted network meta-analysis. Cochrane Database syst. Rev., 3, 2017, CD011343.
157. Centuoriand, S.M., Martinez, J.D., Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer. Dig. Dis. Sci. 59 (2014), 2367–2380.
158. Feldmanand, R., Martinez, J.D., Growth suppression by ursodeoxycholic acid involves caveolin-1 enhanced degradation of EGFR. Biochim. Biophys. Acta 1793 (2009), 1387–1394.
159. Akare, S., Jean-Louis, S., Chen, W., Wood, D.J., Powell, A.A., Martinez, J.D., Ursodeoxycholic acid modulates histone acetylation and induces differentiation and senescence. Int. J. Cancer 119 (2006), 2958–2969.
160. Weh, K.M., Clarke, J., Kresty, L.A., Cranberries and cancer: an update of preclinical studies evaluating the cancer inhibitory potential of cranberry and cranberry derived constituents. Antioxidants, 5, 2016.
161. Chen, I.H., Lu, M.C., Du, Y.C., Yen, M.H., Wu, C.C., Chen, Y.H., Hung, C.S., Chen, S.L., Chang, F.R., Wu, Y.C., Cytotoxic triterpenoids from the stems of Microtropis japonica. J. Nat. Prod. 72 (2009), 1231–1236.
162. Kim, H., Ramirez, C.N., Su, Z.Y., Kong, A.N., Epigenetic modifications of triterpenoid ursolic acid in activating Nrf2 and blocking cellular transformation of mouse epidermal cells. J. Nutr. Biochem. 33 (2016), 54–62.
163. Bezerra, D.P., Soares, A.K., de Sousa, D.P., Overview of the role of vanillin on redox status and cancer development. Oxid. Med. Cell. Longevity, 2016, 2016, 9734816.
164. Seidel, C., Schnekenburger, M., Mazumder, A., Teiten, M.H., Kirsch, G., Dicato, M., Diederich, M., 4-Hydroxybenzoic acid derivatives as HDAC6-specific inhibitors modulating microtubular structure and HSP90alpha chaperone activity against prostate cancer. Biochem. Pharmacol. 99 (2016), 31–52.
165. Gaisina, I.N., Tueckmantel, W., Ugolkov, A., Shen, S., Hoffen, J., Dubrovskyi, O., Mazar, A., Schoon, R.A., Billadeau, D., Kozikowski, A.P., Identification of HDAC6-Selective inhibitors of low cancer cell cytotoxicity. ChemMedChem 11 (2016), 81–92.
166. Hideshima, T., Qi, J., Paranal, R.M., Tang, W., Greenberg, E., West, N., Colling, M.E., Estiu, G., Mazitschek, R., Perry, J.A., Ohguchi, H., Cottini, F., Mimura, N., Gorgun, G., Tai, Y.T., Richardson, P.G., Carrasco, R.D., Wiest, O., Schreiber, S.L., Anderson, K.C., Bradner, J.E., Discovery of selective small-molecule HDAC6 inhibitor for overcoming proteasome inhibitor resistance in multiple myeloma. Proc. Natl. Acad. Sci. U. S. A. 113 (2016), 13162–13167.
167. Lienlaf, M., Perez-Villarroel, P., Knox, T., Pabon, M., Sahakian, E., Powers, J., Woan, K.V., Lee, C., Cheng, F., Deng, S., Smalley, K.S., Montecino, M., Kozikowski, A., Pinilla-Ibarz, J., Sarnaik, A., Seto, E., Weber, J., Sotomayor, E.M., Villagra, A., Essential role of HDAC6 in the regulation of PD-L1 in melanoma. Mol. Oncol. 10 (2016), 735–750.
168. Falkenbergand, K.J., Johnstone, R.W., Histone deacetylases and their inhibitors in cancer: neurological diseases and immune disorders. Nat. Rev. Drug Discov. 13 (2014), 673–691.
169. Bradbury, C.A., Khanim, F.L., Hayden, R., Bunce, C.M., White, D.A., Drayson, M.T., Craddock, C., Turner, B.M., Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia 19 (2005), 1751–1759.
170. Moreno, D.A., Scrideli, C.A., Cortez, M.A., de Paula Queiroz, R., Valera, E.T., da Silva Silveira, V., Yunes, J.A., Brandalise, S.R., Tone, L.G., Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia. Br. J. Haematol. 150 (2010), 665–673.
171. Zhang, Z., Yamashita, H., Toyama, T., Sugiura, H., Omoto, Y., Ando, Y., Mita, K., Hamaguchi, M., Hayashi, S., Iwase, H., HDAC6 expression is correlated with better survival in breast cancer. Clin. Cancer Res. 10 (2004), 6962–6968.
172. Yoshida, N., Omoto, Y., Inoue, A., Eguchi, H., Kobayashi, Y., Kurosumi, M., Saji, S., Suemasu, K., Okazaki, T., Nakachi, K., Fujita, T., Hayashi, S., Prediction of prognosis of estrogen receptor-positive breast cancer with combination of selected estrogen-regulated genes. Cancer Sci. 95 (2004), 496–502.
173. Gradilone, S.A., Radtke, B.N., Bogert, P.S., Huang, B.Q., Gajdos, G.B., LaRusso, N.F., HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res. 73 (2013), 2259–2270.
174. Van Damme, M., Crompot, E., Meuleman, N., Mineur, P., Bron, D., Lagneaux, L., Stamatopoulos, B., HDAC isoenzyme expression is deregulated in chronic lymphocytic leukemia B-cells and has a complex prognostic significance. Epigenetics 7 (2012), 1403–1412.
175. Marquard, L., Gjerdrum, L.M., Christensen, I.J., Jensen, P.B., Sehested, M., Ralfkiaer, E., Prognostic significance of the therapeutic targets histone deacetylase 1, 2, 6 and acetylated histone H4 in cutaneous T-cell lymphoma. Histopathology 53 (2008), 267–277.
176. Jung, K.H., Noh, J.H., Kim, J.K., Eun, J.W., Bae, H.J., Chang, Y.G., Kim, M.G., Park, W.S., Lee, J.Y., Lee, S.Y., Chu, I.S., Nam, S.W., Histone deacetylase 6 functions as a tumor suppressor by activating c-Jun NH2-terminal kinase-mediated beclin 1-dependent autophagic cell death in liver cancer. Hepatology 56 (2012), 644–657.
177. Bai, J., Lei, Y., An, G.L., He, L., Down-regulation of deacetylase HDAC6 inhibits the melanoma cell line A375. S2 growth through ROS-dependent mitochondrial pathway. PLoS One, 10, 2015, e0121247.
178. Sakuma, T., Uzawa, K., Onda, T., Shiiba, M., Yokoe, H., Shibahara, T., Tanzawa, H., Aberrant expression of histone deacetylase 6 in oral squamous cell carcinoma. Int. J. Oncol. 29 (2006), 117–124.
179. Witt, O., Deubzer, H.E., Milde, T., Oehme, I., HDAC family: what are the cancer relevant targets?. Cancer Lett. 277 (2009), 8–21.
180. Bazzaro, M., Lin, Z., Santillan, A., Lee, M.K., Wang, M.C., Chan, K.C., Bristow, R.E., Mazitschek, R., Bradner, J., Roden, R.B., Ubiquitin proteasome system stress underlies synergistic killing of ovarian cancer cells by bortezomib and a novel HDAC6 inhibitor. Clin. Cancer Res. 14 (2008), 7340–7347.
181. Rosik, L., Niegisch, G., Fischer, U., Jung, M., Schulz, W.A., Hoffmann, M.J., Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells. Cancer. Biol. Ther. 15 (2014), 742–757.
182. Yoo, J., Kim, S.J., Son, D., Seo, H., Baek, S.Y., Maeng, C.Y., Lee, C., Kim, I.S., Jung, Y.H., Lee, S.M., Park, H.J., Computer-aided identification of new histone deacetylase 6 selective inhibitor with anti-sepsis activity. Eur. J. Med. Chem. 116 (2016), 126–135.
183. Wang, L., Kofler, M., Brosch, G., Melesina, J., Sippl, W., Martinez, E.D., Easmon, J., 2-Benzazolyl-4-Piperazin-1-Ylsulfonylbenzenecarbohydroxamic acids as novel selective histone deacetylase-6 inhibitors with antiproliferative activity. PLoS One, 10, 2015, e0134556.
184. Lee, H.Y., Lee, J.F., Kumar, S., Wu, Y.W., HuangFu, W.C., Lai, M.J., Li, Y.H., Huang, H.L., Kuo, F.C., Hsiao, C.J., Cheng, C.C., Yang, C.R., Liou, J.P., 3-Aroylindoles display antitumor activity in vitro and in vivo: effects of N1-substituents on biological activity. Eur. J. Med. Chem. 125 (2017), 1268–1278.
185. Blackburn, C., Barrett, C., Chin, J., Garcia, K., Gigstad, K., Gould, A., Gutierrez, J., Harrison, S., Hoar, K., Lynch, C., Rowland, R.S., Tsu, C., Ringeling, J., Xu, H., Potent histone deacetylase inhibitors derived from 4-(aminomethyl)-N-hydroxybenzamide with high selectivity for the HDAC6 isoform. J. Med. Chem. 56 (2013), 7201–7211.
186. Ryu, H.W., Shin, D.H., Lee, D.H., Choi, J., Han, G., Lee, K.Y., Kwon, S.H., HDAC6 deacetylates p53 at lysines 381/382 and differentially coordinates p53-induced apoptosis. Cancer Lett. 391 (2017), 162–171.
187. Choi, E., Lee, C., Park, J.E., Seo, J.J., Cho, M., Kang, J.S., Kim, H.M., Park, S.K., Lee, K., Han, G., Structure and property based design, synthesis and biological evaluation of gamma-lactam based HDAC inhibitors. Bioorg. Med. Chem. Lett. 21 (2011), 1218–1221.
188. Krukowski, K., Ma, J., Golonzhka, O., Laumet, G.O., Gutti, T., van Duzer, J.H., Mazitschek, R., Jarpe, M.B., Heijnen, C.J., Kavelaars, A., HDAC6 inhibition effectively reverses chemotherapy-induced peripheral neuropathy. Pain 158 (2017), 1126–1137.
189. Jochems, J., Teegarden, S.L., Chen, Y., Boulden, J., Challis, C., Ben-Dor, G.A., Kim, S.F., Berton, O., Enhancement of stress resilience through histone deacetylase 6-mediated regulation of glucocorticoid receptor chaperone dynamics. Biol. Psychiatry 77 (2015), 345–355.
190. Jochems, J., Boulden, J., Lee, B.G., Blendy, J.A., Jarpe, M., Mazitschek, R., Van Duzer, J.H., Jones, S., Berton, O., Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology 39 (2014), 389–400.
191. Lin, X., Chen, W., Qiu, Z., Guo, L., Zhu, W., Li, W., Wang, Z., Zhang, W., Zhang, Z., Rong, Y., Zhang, M., Yu, L., Zhong, S., Zhao, R., Wu, X., Wong, J.C., Tang, G., Design and synthesis of orally bioavailable aminopyrrolidinone histone deacetylase 6 inhibitors. J. Med. Chem. 58 (2015), 2809–2820.
192. Lee, H.Y., Tsai, A.C., Chen, M.C., Shen, P.J., Cheng, Y.C., Kuo, C.C., Pan, S.L., Liu, Y.M., Liu, J.F., Yeh, T.K., Wang, J.C., Chang, C.Y., Chang, J.Y., Liou, J.P., Azaindolylsulfonamides, with a more selective inhibitory effect on histone deacetylase 6 activity, exhibit antitumor activity in colorectal cancer HCT116 cells. J. Med. Chem. 57 (2014), 4009–4022.
193. Kozikowski, A.P., Chen, Y., Gaysin, A.M., Savoy, D.N., Billadeau, D.D., Kim, K.H., Chemistry, biology, and QSAR studies of substituted biaryl hydroxamates and mercaptoacetamides as HDAC inhibitors-nanomolar-potency inhibitors of pancreatic cancer cell growth. ChemMedChem 3 (2008), 487–501.
194. Shen, S., Benoy, V., Bergman, J.A., Kalin, J.H., Frojuello, M., Vistoli, G., Haeck, W., Van Den Bosch, L., Kozikowski, A.P., Bicyclic-capped histone deacetylase 6 inhibitors with improved activity in a model of axonal charcot-marie-Tooth disease. ACS Chem. Neurosci. 7 (2016), 240–258.
195. Schafer, S., Saunders, L., Eliseeva, E., Velena, A., Jung, M., Schwienhorst, A., Strasser, A., Dickmanns, A., Ficner, R., Schlimme, S., Sippl, W., Verdin, E., Jung, M., Phenylalanine-containing hydroxamic acids as selective inhibitors of class IIb histone deacetylases (HDACs). Bioorg. Med. Chem. 16 (2008), 2011–2033.
196. Choi, S.E., Weerasinghe, S.V., Pflum, M.K., The structural requirements of histone deacetylase inhibitors: suberoylanilide hydroxamic acid analogs modified at the C3 position display isoform selectivity. Bioorg. Med. Chem. Lett. 21 (2011), 6139–6142.
197. Kaliszczak, M., Trousil, S., Aberg, O., Perumal, M., Nguyen, Q.D., Aboagye, E.O., A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth. Br. J. Cancer 108 (2013), 342–350.
198. Wagner, F.F., Olson, D.E., Gale, J.P., Kaya, T., Weiwer, M., Aidoud, N., Thomas, M., Davoine, E.L., Lemercier, B.C., Zhang, Y.L., Holson, E.B., Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif. J. Med. Chem. 56 (2013), 1772–1776.
199. Kozikowski, A.P., Tapadar, S., Luchini, D.N., Kim, K.H., Billadeau, D.D., Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6. J. Med. Chem. 51 (2008), 4370–4373.
200. Smil, D.V., Manku, S., Chantigny, Y.A., Leit, S., Wahhab, A., Yan, T.P., Fournel, M., Maroun, C., Li, Z., Lemieux, A.M., Nicolescu, A., Rahil, J., Lefebvre, S., Panetta, A., Besterman, J.M., Deziel, R., Novel HDAC6 isoform selective chiral small molecule histone deacetylase inhibitors. Bioorg. Med. Chem. Lett. 19 (2009), 688–692.
201. Huang, P., Almeciga-Pinto, I., Jarpe, M., van Duzer, J.H., Mazitschek, R., Yang, M., Jones, S.S., Quayle, S.N., Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models. Oncotarget 8 (2017), 2694–2707.
202. North, B.J., Almeciga-Pinto, I., Tamang, D., Yang, M., Jones, S.S., Quayle, S.N., Enhancement of pomalidomide anti-tumor response with ACY-241, a selective HDAC6 inhibitor. PLoS One, 12, 2017, e0173507.
203. Gupta, P.K., Reid, R.C., Liu, L., Lucke, A.J., Broomfield, S.A., Andrews, M.R., Sweet, M.J., Fairlie, D.P., Inhibitors selective for HDAC6 in enzymes and cells. Bioorg. Med. Chem. Lett. 20 (2010), 7067–7070.
204. Olsenand, C.A., Ghadiri, M.R., Discovery of potent and selective histone deacetylase inhibitors via focused combinatorial libraries of cyclic alpha3beta-tetrapeptides. J. Med. Chem. 52 (2009), 7836–7846.
205. Ellis, J.D., Neil, D.A., Inston, N.G., Jenkinson, E., Drayson, M.T., Hampson, P., Shuttleworth, S.J., Ready, A.R., Cobbold, M., Inhibition of histone deacetylase 6 reveals a potent immunosuppressant effect in models of transplantation. Transplantation 100 (2016), 1667–1674.
206. Yang, Z., Wang, T., Wang, F., Niu, T., Liu, Z., Chen, X., Long, C., Tang, M., Cao, D., Wang, X., Xiang, W., Yi, Y., Ma, L., You, J., Chen, L., Discovery of selective histone deacetylase 6 inhibitors using the quinazoline as the cap for the treatment of cancer. J. Med. Chem. 59 (2016), 1455–1470.
207. Bergman, J.A., Woan, K., Perez-Villarroel, P., Villagra, A., Sotomayor, E.M., Kozikowski, A.P., Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth. J. Med. Chem. 55 (2012), 9891–9899.
208. Sternson, S.M., Wong, J.C., Grozinger, C.M., Schreiber, S.L., Synthesis of 7200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin. Org. Lett. 3 (2001), 4239–4242.
209. Auzzas, L., Larsson, A., Matera, R., Baraldi, A., Deschenes-Simard, B., Giannini, G., Cabri, W., Battistuzzi, G., Gallo, G., Ciacci, A., Vesci, L., Pisano, C., Hanessian, S., Non-natural macrocyclic inhibitors of histone deacetylases: design, synthesis, and activity. J. Med. Chem. 53 (2010), 8387–8399.
210. Senger, J., Melesina, J., Marek, M., Romier, C., Oehme, I., Witt, O., Sippl, W., Jung, M., Synthesis and biological investigation of oxazole hydroxamates as highly selective histone deacetylase 6 (HDAC6) inhibitors. J. Med. Chem. 59 (2016), 1545–1555.
211. Sodji, Q.H., Kornacki, J.R., McDonald, J.F., Mrksich, M., Oyelere, A.K., Design and structure activity relationship of tumor-homing histone deacetylase inhibitors conjugated to folic and pteroic acids. Eur. J. Med. Chem. 96 (2015), 340–359.
212. Schafer, S., Saunders, L., Schlimme, S., Valkov, V., Wagner, J.M., Kratz, F., Sippl, W., Verdin, E., Jung, M., Pyridylalanine-containing hydroxamic acids as selective HDAC6 inhibitors. ChemMedChem 4 (2009), 283–290.
213. Liu, Y.M., Lee, H.Y., Lai, M.J., Pan, S.L., Huang, H.L., Kuo, F.C., Chen, M.C., Liou, J.P., Pyrimidinedione-mediated selective histone deacetylase 6 inhibitors with antitumor activity in colorectal cancer HCT116 cells. Org. Biomol. Chem. 13 (2015), 10226–10235.
214. Valente, S., Trisciuoglio, D., Tardugno, M., Benedetti, R., Labella, D., Secci, D., Mercurio, C., Boggio, R., Tomassi, S., Di Maro, S., Novellino, E., Altucci, L., Del Bufalo, D., Mai, A., Cosconati, S., tert-Butylcarbamate-containing histone deacetylase inhibitors: apoptosis induction, cytodifferentiation, and antiproliferative activities in cancer cells. ChemMedChem 8 (2013), 800–811.
215. Yu, C.W., Chang, P.T., Hsin, L.W., Chern, J.W., Quinazolin-4-one derivatives as selective histone deacetylase-6 inhibitors for the treatment of Alzheimer's disease. J. Med. Chem. 56 (2013), 6775–6791.
216. Santo, L., Hideshima, T., Kung, A.L., Tseng, J.C., Tamang, D., Yang, M., Jarpe, M., van Duzer, J.H., Mazitschek, R., Ogier, W.C., Cirstea, D., Rodig, S., Eda, H., Scullen, T., Canavese, M., Bradner, J., Anderson, K.C., Jones, S.S., Raje, N., Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood 119 (2012), 2579–2589.
217. Peng, U., Wang, Z., Pei, S., Ou, Y., Hu, P., Liu, W., Song, J., ACY-1215 accelerates vemurafenib induced cell death of BRAF-mutant melanoma cells via induction of ER stress and inhibition of ERK activation. Oncol. Rep. 37 (2017), 1270–1276.
218. Amengual, J.E., Johannet, P., Lombardo, M., Zullo, K., Hoehn, D., Bhagat, G., Scotto, L., Jirau-Serrano, X., Radeski, D., Heinen, J., Jiang, H., Cremers, S., Zhang, Y., Jones, S., O'Connor, O.A., Dual targeting of protein degradation pathways with the selective HDAC6 inhibitor ACY-1215 and bortezomib is synergistic in lymphoma. Clin. Cancer Res. 21 (2015), 4663–4675.
219. Amengual, J.E., Prabhu, S.A., Lombardo, M., Zullo, K., Johannet, P.M., Gonzalez, Y., Scotto, L., Serrano, X.J., Wei, Y., Duong, J., Nandakumar, R., Cremers, S., Verma, A., Elemento, O., O'Connor, O.A., Mechanisms of acquired drug resistance to the HDAC6 selective inhibitor ricolinostat reveals rational drug-drug combination with ibrutinib. Clin. Cancer Res. 23 (2016), 3084–3096.
220. Yee, A.J., Bensinger, W.I., Supko, J.G., Voorhees, P.M., Berdeja, J.G., Richardson, P.G., Libby, E.N., Wallace, E.E., Birrer, N.E., Burke, J.N., Tamang, D.L., Yang, M., Jones, S.S., Wheeler, C.A., Markelewicz, R.J., Raje, N.S., Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a multicentre phase 1b trial. Lancet Oncol. 17 (2016), 1569–1578.
221. Das, D.S., Das, A., Ray, A., Song, Y., Samur, M.K., Munshi, N.C., Chauhan, D., Anderson, K.C., Blockade of deubiquitylating enzyme USP1 inhibits DNA repair and triggers apoptosis in multiple myeloma cells. Clin. Cancer Res., 2017.
222. Dasmahapatra, G., Patel, H., Friedberg, J., Quayle, S.N., Jones, S.S., Grant, S., In vitro and in vivo interactions between the HDAC6 inhibitor ricolinostat (ACY1215) and the irreversible proteasome inhibitor carfilzomib in non-Hodgkin lymphoma cells. Mol. Cancer Ther. 13 (2014), 2886–2897.
223. Mishima, Y., Santo, L., Eda, H., Cirstea, D., Nemani, N., Yee, A.J., O'Donnell, E., Selig, M.K., Quayle, S.N., Arastu-Kapur, S., Kirk, C., Boise, L.H., Jones, S.S., Raje, N., Ricolinostat (ACY-1215) induced inhibition of aggresome formation accelerates carfilzomib-induced multiple myeloma cell death. Br. J. Haematol. 169 (2015), 423–434.
224. Nepali, K., Lee, H.Y., Lai, M.J., Ojha, R., Wu, T.Y., Wu, G.X., Chen, M.C., Liou, J.P., Ring-opened tetrahydro-gamma-carbolines display cytotoxicity and selectivity with histone deacetylase isoforms. Eur. J. Med. Chem. 127 (2017), 115–127.
225. Scott, G.K., Marx, C., Berger, C.E., Saunders, L.R., Verdin, E., Schafer, S., Jung, M., Benz, C.C., Destabilization of ERBB2 transcripts by targeting 3’ untranslated region messenger RNA associated HuR and histone deacetylase-6. Mol. Cancer Res.: MCR 6 (2008), 1250–1258.
226. Hackanson, B., Rimmele, L., Benkisser, M., Abdelkarim, M., Fliegauf, M., Jung, M., Lubbert, M., HDAC6 as a target for antileukemic drugs in acute myeloid leukemia. Leuk. Res. 36 (2012), 1055–1062.
227. Chen, Y., Lopez-Sanchez, M., Savoy, D.N., Billadeau, D.D., Dow, G.S., Kozikowski, A.P., A series of potent and selective, triazolylphenyl-based histone deacetylases inhibitors with activity against pancreatic cancer cells and Plasmodium falciparum. J. Med. Chem. 51 (2008), 3437–3448.
228. Hideshima, T., Bradner, J.E., Wong, J., Chauhan, D., Richardson, P., Schreiber, S.L., Anderson, K.C., Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 8567–8572.
229. Komatsu, S., Moriya, S., Che, X.F., Yokoyama, T., Kohno, N., Miyazawa, K., Combined treatment with SAHA, bortezomib, and clarithromycin for concomitant targeting of aggresome formation and intracellular proteolytic pathways enhances ER stress-mediated cell death in breast cancer cells. Biochem. Biophys. Res. Commun. 437 (2013), 41–47.
230. De Vreese, R., Verhaeghe, T., Desmet, T., D'Hooghe, M., Potent and selective HDAC6 inhibitory activity of N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes as novel sulfur analogues of Tubastatin A. Chem. Commun. 49 (2013), 3775–3777.
231. Goracci, L., Deschamps, N., Randazzo, G.M., Petit, C., Dos Santos Passos, C., Carrupt, P.A., Simoes-Pires, C., Nurisso, A., A rational approach for the identification of non-Hydroxamate HDAC6-Selective inhibitors. Sci. Rep., 6, 2016, 29086.
232. Patil, V., Sodji, Q.H., Kornacki, J.R., Mrksich, M., Oyelere, A.K., 3-Hydroxypyridin-2-thione as novel zinc binding group for selective histone deacetylase inhibition. J. Med. Chem. 56 (2013), 3492–3506.
233. Ontoria, J.M., Altamura, S., Di Marco, A., Ferrigno, F., Laufer, R., Muraglia, E., Palumbi, M.C., Rowley, M., Scarpelli, R., Schultz-Fademrecht, C., Serafini, S., Steinkuhler, C., Jones, P., Identification of novel, selective, and stable inhibitors of class II histone deacetylases. Validation studies of the inhibition of the enzymatic activity of HDAC4 by small molecules as a novel approach for cancer therapy. J. Med. Chem. 52 (2009), 6782–6789.
234. Suzuki, T., Kouketsu, A., Itoh, Y., Hisakawa, S., Maeda, S., Yoshida, M., Nakagawa, H., Miyata, N., Highly potent and selective histone deacetylase 6 inhibitors designed based on a small-molecular substrate. J. Med. Chem. 49 (2006), 4809–4812.
235. Kozikowski, A.P., Chen, Y., Gaysin, A., Chen, B., D'Annibale, M.A., Suto, C.M., Langley, B.C., Functional differences in epigenetic modulators-superiority of mercaptoacetamide-based histone deacetylase inhibitors relative to hydroxamates in cortical neuron neuroprotection studies. J. Med. Chem. 50 (2007), 3054–3061.
236. Kalin, J.H., Zhang, H., Gaudrel-Grosay, S., Vistoli, G., Kozikowski, A.P., Chiral mercaptoacetamides display enantioselective inhibition of histone deacetylase 6 and exhibit neuroprotection in cortical neuron models of oxidative stress. ChemMedChem 7 (2012), 425–439.
237. Inks, E.S., Josey, B.J., Jesinkey, S.R., Chou, C.J., A novel class of small molecule inhibitors of HDAC6. ACS Chem. Biol. 7 (2012), 331–339.
238. Itoh, T., Suzuki, A., Kouketsu, N., Suzuki, S., Maeda, M., Nakagawa, H., Miyata, N., Design, synthesis, structure–selectivity relationship, and effect on human cancer cells of a novel series of histone deacetylase 6-selective inhibitors. J. Med. Chem. 50 (2007), 5425–5438.