N. M. Archin, A. L. Liberty, A. D. Kashuba, S. K. Choudhary, J. D. Kuruc et al., Margolis, Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy, Nature, vol.487, pp.482-485, 2012.

G. Lehrman, I. B. Hogue, S. Palmer, C. Jennings, C. A. Spina et al., Depletion of latent HIV-1 infection in vivo: a proof-ofconcept study, The Lancet, vol.366, pp.67098-67103, 2005.

D. G. Wei, V. Chiang, E. Fyne, M. Balakrishnan, T. Barnes et al., Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing, PLoS Pathog, vol.10, p.1004071, 2014.

J. Roche and P. Bertrand, Inside HDACs with more selective HDAC inhibitors, Eur. J. Med. Chem, vol.121, pp.451-483, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01505640

P. Bertrand, Inside HDAC with HDAC inhibitors, Eur. J. Med. Chem, vol.45, pp.2095-2116, 2010.
URL : https://hal.archives-ouvertes.fr/hal-01505640

P. A. Marks, Discovery and development of SAHA as an anticancer agent, Oncogene, vol.26, pp.1351-1356

R. Poole, Belinostat: First Global Approval, Drugs, vol.74, pp.1543-1554, 2014.

P. G. Richardson, J. P. Laubach, S. Lonial, P. Moreau, and S. ,

V. T. Yoon, M. A. Hungria, M. Dimopoulos, M. Beksac, J. F. Alsina et al., Panobinostat: a novel pandeacetylase inhibitor for the treatment of relapsed or relapsed and refractory multiple myeloma, Expert Rev. Anticancer Ther, vol.15, pp.737-748, 2015.

T. Vanhaecke, P. Papeleu, G. Elaut, and V. Rogiers, Trichostatin A-like Hydroxamate Histone Deacetylase Inhibitors as Therapeutic Agents: Toxicological Point of View, Curr. Med. Chem, vol.11, pp.1629-1643, 2004.

M. Mottamal, S. Zheng, T. L. Huang, and G. Wang, Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents, Molecules, vol.20, p.3898, 2015.

C. Grant, F. Rahman, R. Piekarz, C. Peer, R. Frye et al., Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors, Expert Rev. Anticancer Ther, vol.10, pp.997-1008, 2010.

S. P. Iyer and F. F. Foss, Romidepsin for the Treatment of Peripheral T-Cell Lymphoma, The Oncologist, vol.20, pp.1084-1091, 2015.

W. K. Kelly, O. A. O'connor, L. M. Krug, J. H. Chiao, M. Heaney et al., Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer, J Clin Oncol, vol.23, pp.3923-3954, 2005.

E. H. Rubin, N. G. Agrawal, E. J. Friedman, P. Scott, K. E. Mazina et al., A study to determine the effects of food and multiple dosing on the pharmacokinetics of vorinostat given orally to patients with advanced cancer, Clin Cancer Res, vol.12, pp.7039-7084, 2006.

B. S. Mann, J. R. Johnson, M. H. Cohen, R. Justice, and R. Pazdur, FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma, Oncologist, vol.12, pp.1247-52, 2007.

L. M. Krug, H. L. Kindler, H. Calvert, C. Manegold, A. S. Tsao et al., Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial, Lancet Oncol, vol.16, pp.447-56, 2015.

H. Nakajima, Y. B. Kim, H. Terano, M. Yoshida, and S. , Horinouchi, FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor, Exp Cell Res, vol.241, pp.126-159, 1998.

V. Sandor, S. Bakke, R. W. Robey, M. H. Kang, M. V. Blagosklonny et al., Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasms, vol.8, pp.718-746, 2002.

D. S. Schrump, M. R. Fischette, D. M. Nguyen, M. Zhao, X. Li et al., Clinical and molecular responses in lung cancer patients receiving Romidepsin, Clin Cancer Res, vol.14, pp.188-98, 2008.

R. L. Piekarz, R. Frye, M. Turner, J. J. Wright, S. L. Allen et al., Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma, J Clin Oncol, vol.27, pp.5410-5417, 2009.

B. Coiffier, B. Pro, H. M. Prince, F. Foss, L. Sokol et al., Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy, J Clin Oncol, vol.30, pp.631-637, 2012.

C. Grant, F. Rahman, R. Piekarz, C. Peer, R. Frye et al., Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors, Expert Rev Anticancer Ther, vol.10, pp.997-1008, 2010.

R. M. Poole, Belinostat: first global approval, Drugs, vol.74, pp.1543-54, 2014.

U. Lassen, L. R. Molife, M. Sorensen, S. A. Engelholm, L. Vidal et al., A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours, Br J Cancer, vol.103, pp.12-19, 2010.

N. L. Steele, J. A. Plumb, L. Vidal, J. Tjornelund, P. Knoblauch et al., Pharmacokinetic and pharmacodynamic properties of an oral formulation of the histone deacetylase inhibitor Belinostat (PXD101), Cancer Chemother Pharmacol, vol.67, pp.1273-1282, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00615339

W. Yeo, H. C. Chung, S. L. Chan, L. Z. Wang, R. Lim et al.,

J. H. Chan, C. Tong, A. T. Erlichman, B. C. Chan, and . Goh, Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter phase I/II study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group, J Clin Oncol, vol.30, pp.3361-3368, 2012.

O. A. O'connor, S. Horwitz, T. Masszi, A. Van-hoof, P. Brown et al., Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study, J Clin Oncol, vol.33, pp.2492-2501, 2015.

F. Foss, R. Advani, M. Duvic, K. B. Hymes, T. Intragumtornchai et al., A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma, Br J Haematol, vol.168, pp.811-820, 2015.

N. L. Steele, J. A. Plumb, L. Vidal, J. Tjornelund, P. Knoblauch et al., A phase 1 pharmacokinetic and pharmacodynamic study of the histone deacetylase inhibitor belinostat in patients with advanced solid tumors, Clin Cancer Res, vol.14, pp.804-814, 2008.

S. S. Ramalingam, C. P. Belani, C. Ruel, P. Frankel, B. Gitlitz et al., Phase II study of belinostat (PXD101), a histone deacetylase inhibitor, for second line therapy of advanced malignant pleural mesothelioma, J Thorac Oncol, vol.4, pp.97-101, 2009.

F. Giles, T. Fischer, J. Cortes, G. Garcia-manero, J. Beck et al., A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies, Clin Cancer Res, vol.12, pp.4628-4663, 2006.

S. Morita, S. Oizumi, H. Minami, K. Kitagawa, Y. Komatsu et al., Phase I dose-escalating study of panobinostat (LBH589) administered intravenously to Japanese patients with advanced solid tumors, Invest New Drugs, vol.30, pp.1950-1957, 2012.

S. Sharma, P. O. Witteveen, M. P. Lolkema, D. Hess, H. Gelderblom et al.,

S. Valera and . Mu, A phase I, open-label, multicenter study to evaluate the pharmacokinetics and safety of oral panobinostat in patients with advanced solid tumors and varying degrees of renal function, Cancer Chemother Pharmacol, vol.75, pp.87-95, 2015.

A. Younes, A. Sureda, D. Ben-yehuda, P. L. Zinzani, T. C. Ong et al., Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: reEpigenetic Metalloenzymes Current Medicinal Chemistry, vol.25, p.27, 2018.

, sults of a phase II study, J Clin Oncol, vol.30, pp.2197-203, 2012.

J. F. San-miguel, V. T. Hungria, S. S. Yoon, M. Beksac, M. A. Dimopoulos et al., Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial, Lancet Oncol, vol.15, pp.1195-206, 2014.

Z. Qiao, S. Ren, W. Li, X. Wang, M. He et al., Chidamide, a novel histone deacetylase inhibitor, synergistically enhances gemcitabine cytotoxicity in pancreatic cancer cells, Biochem. Biophys. Res. Commun, vol.434, pp.95-101, 2013.

A. Saito, T. Yamashita, Y. Mariko, Y. Nosaka, K. Tsuchiya et al., A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors, Proc Natl Acad Sci U A, vol.96, pp.4592-4599, 1999.

Q. C. Ryan, D. Headlee, M. Acharya, A. Sparreboom, J. B. Trepel et al., Phase I and pharmacokinetic study of MS275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma, J Clin Oncol, vol.23, 2005.

C. L. Batlevi, Y. Kasamon, R. G. Bociek, P. Lee, L. Gore et al., ENGAGE-501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma, Haematologica, vol.101, pp.968-975, 2016.

M. Lobera, K. P. Madauss, D. T. Pohlhaus, Q. G. Wright, M. Trocha et al., Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group, Nat. Chem. Biol, vol.9, pp.319-325, 2013.
DOI : 10.1038/nchembio.1223

A. M. Evens, S. Balasubramanian, J. M. Vose, W. Harb, L. I. Gordon et al., A Phase I/II Multicenter, Open-Label Study of the Oral Histone Deacetylase Inhibitor Abexinostat in Relapsed/Refractory Lymphoma, Clin. Cancer Res, vol.22, p.1059, 2016.

N. Rivera, -. Valle, S. Gao, C. P. Miller, J. Fulbright et al., PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells, Int. J. Cell Biol, p.207420, 2010.

J. J. Buggy, Z. A. Cao, K. E. Bass, E. Verner, S. Balasubramanian et al., CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo, Mol. Cancer Ther, vol.5, pp.1309-1317, 2006.

V. Novotny-diermayr, K. Sangthongpitag, C. Y. Hu, X. Wu, N. Sausgruber et al., SB939, a Novel Potent and Orally Active Histone Deacetylase Inhibitor with High Tumor Exposure and Efficacy in Mouse Models of Colorectal Cancer, Mol. Cancer Ther, vol.9, p.642, 2010.

V. Novotny-diermayr, N. Sausgruber, Y. K. Loh, M. K. Pasha, R. Jayaraman et al., Pharmacodynamic Evaluation of the Target Efficacy of SB939, an Oral HDAC Inhibitor with Selectivity for Tumor Tissue, Mol. Cancer Ther, vol.10, p.1207, 2011.

V. Novotny-diermayr, K. Sangthongpitag, C. Y. Hu, X. Wu, N. Sausgruber et al., SB939, a Novel Potent and Orally Active Histone Deacetylase Inhibitor with High Tumor Exposure and Efficacy in Mouse Models of Colorectal Cancer, Mol. Cancer Ther, vol.9, pp.642-652, 2010.

W. Tong, Y. Wei, W. Stevenson, S. Kuang, Z. Fang et al., Preclinical antileukemia activity of JNJ-26481585, a potent second-generation histone deacetylase inhibitor, Leuk. Res, vol.34, pp.221-228, 2010.
DOI : 10.1016/j.leukres.2009.07.024

F. Child, P. L. Ortiz-romero, R. Alvarez, M. Bagot, R. Stadler et al., Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome, Br. J. Dermatol, vol.175, pp.80-88, 2016.

L. Bao, H. Diao, N. Dong, X. Su, B. Wang et al., Histone deacetylase inhibitor induces cell apoptosis and cycle arrest in lung cancer cells via mitochondrial injury and p53 up-acetylation, Cell Biol. Toxicol, vol.32, p.469, 2016.
DOI : 10.1007/s10565-016-9347-8

URL : http://doi.org/10.1007/s10565-016-9347-8

J. Arts, P. King, A. Mariën, W. Floren, A. Beliën et al., JNJ-26481585, a Novel "SecondGeneration" Oral Histone Deacetylase Inhibitor, Shows Broad-Spectrum Preclinical Antitumoral Activity, Clin. Cancer Res, vol.15, p.6841, 2009.
DOI : 10.1158/1078-0432.ccr-09-0547

URL : http://clincancerres.aacrjournals.org/content/clincanres/15/22/6841.full.pdf

A. J. Yee, W. I. Bensinger, J. G. Supko, P. M. Voorhees, J. G. Berdeja et al., Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a multicentre phase 1b trial, Lancet Oncol, vol.17, issue.16, pp.30375-30383, 2016.
DOI : 10.1016/s1470-2045(16)30375-8

L. Santo, T. Hideshima, A. L. Kung, J. Tseng, D. Tamang et al., Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in Blanquart et al. combination with bortezomib in multiple myeloma, Blood, vol.119, p.2579, 2012.

T. Hideshima, J. E. Bradner, J. Wong, D. Chauhan, P. Richardson et al., Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma, Proc. Natl. Acad. Sci. U. S. A, vol.102, pp.8567-8572, 2005.

S. T. Nawrocki, J. S. Carew, K. H. Maclean, J. F. Courage, P. Huang et al., Myc regulates aggresome formation, the induction of Noxa, and apoptosis in response to the combination of bortezomib and SAHA, Blood, vol.112, pp.2917-2926, 2008.

S. T. Nawrocki, J. S. Carew, K. H. Maclean, J. F. Courage, P. Huang et al., Myc regulates aggresome formation, the induction of Noxa, and apoptosis in response to the combination of bortezomib and SAHA, Blood, vol.112, p.2917, 2008.

L. Naymagon and M. Abdul-hay, Novel agents in the treatment of multiple myeloma: a review about the future, J. Hematol. Oncol.J Hematol Oncol, vol.9, p.52, 2016.

S. Chhabra, Novel Proteasome Inhibitors and Histone Deacetylase Inhibitors: Progress in Myeloma Therapeutics, p.10, 2017.
DOI : 10.3390/ph10020040

URL : http://www.mdpi.com/1424-8247/10/2/40/pdf

E. Y. Lin, J. G. Jones, P. Li, L. Zhu, K. D. Whitney et al., Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases, Am. J. Pathol, vol.163, issue.10, pp.63568-63575, 2003.

J. L. Guerriero, A. Sotayo, H. E. Ponichtera, J. A. Castrillon, A. L. Pourzia et al., Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages, Nature, vol.543, pp.428-432, 2017.
DOI : 10.1038/nature21409

P. Huang, I. Almeciga-pinto, M. Jarpe, J. H. Van-duzer, R. Mazitschek et al., Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models, Oncotarget, vol.8, pp.2694-2707, 2017.

B. Eickhoff, S. Ruller, T. Laue, G. Kohler, C. Stahl et al., Trichostatin A modulates expression of p21waf1/cip1, Bcl-xL, ID1, ID2, ID3, CRAB2, GATA-2, hsp86 and TFIID/TAFII31 mRNA in human lung adenocarcinoma cells, Biol Chem, vol.381, pp.107-119, 2000.

A. Saito, T. Yamashita, Y. Mariko, Y. Nosaka, K. Tsuchiya et al., A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors, Proc. Natl. Acad. Sci, vol.96, pp.4592-4597, 1999.

J. Y. Shin, H. S. Kim, J. Park, J. B. Park, and J. Y. Lee, Mechanism for inactivation of the KIP family cyclin-dependent kinase inhibitor genes in gastric cancer cells, Cancer Res, vol.60, pp.262-267, 2000.

J. A. Vrana, R. H. Decker, C. R. Johnson, Z. Wang, W. D. Jarvis et al., Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53, Oncogene, vol.18, pp.7016-7041, 1999.

M. Mottamal, S. Zheng, T. L. Huang, and G. Wang, Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents, Molecules, vol.20, pp.3898-941, 2015.
DOI : 10.3390/molecules20033898

URL : http://www.mdpi.com/1420-3049/20/3/3898/pdf

S. Y. Archer, S. Meng, A. Shei, and R. A. , Hodin, p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells, Proc Natl Acad Sci U A, vol.95, pp.6791-6797, 1998.

W. S. El-deiry, T. Tokino, V. E. Velculescu, D. B. Levy, R. Parsons et al., Vogelstein, WAF1, a potential mediator of p53 tumor suppression, Cell, vol.75, pp.817-842, 1993.
DOI : 10.1016/0092-8674(93)90500-p

F. Condorelli, I. Gnemmi, A. Vallario, A. A. Genazzani, and P. L. Canonico, Inhibitors of histone deacetylase (HDAC) restore the p53 pathway in neuroblastoma cells, Br J Pharmacol, vol.153, pp.657-68, 2008.

Y. Zhao, S. Lu, L. Wu, G. Chai, H. Wang et al., Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21(Waf1/Cip1), Mol Cell Biol, vol.26, pp.2782-90, 2006.

C. Y. Gui, L. Ngo, W. S. Xu, V. M. Richon, and P. A. Marks, Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1, Proc Natl Acad Sci U A, vol.101, pp.1241-1247, 2004.

Y. Sowa, T. Orita, S. Minamikawa-hiranabe, T. Mizuno, H. Nomura et al., Sp3, but not Sp1, mediates the transcriptional activation of the p21/WAF1/Cip1 gene promoter by histone deacetylase inhibitor, Cancer Res, vol.59, pp.4266-70, 1999.

K. A. Strait, B. Dabbas, E. H. Hammond, C. T. Warnick, S. J. Iistrup et al., Cell cycle blockade and differentiation of ovarian cancer cells by the histone deacetylase inhibitor trichostatin A are associated with changes in p21, Rb, and Id proteins, Mol Cancer Ther, vol.1, pp.1181-90, 2002.

V. L. Greenberg, J. M. Williams, J. P. Cogswell, M. Mendenhall, and S. G. Zimmer, Histone deacetylase inhibitors promote apoptosis and differential cell cycle arrest in anaplastic thyroid cancer cells, Thyroid, vol.11, pp.315-340, 2001.
DOI : 10.1089/10507250152039046

V. A. Florenes, M. Skrede, K. Jorgensen, and J. M. Nesland, Deacetylase inhibition in malignant melanomas: impact on cell cycle regulation and survival, Melanoma Res, vol.14, pp.173-81, 2004.

T. E. Fandy, S. Shankar, D. D. Ross, E. Sausville, and R. K. Srivastava, Interactive effects of HDAC inhibitors and TRAIL on apoptosis are associated with changes in mitochondrial functions and expressions of cell cycle regulatory genes in multiple myeloma, Neoplasia, vol.7, pp.646-57, 2005.

F. Guo, C. Sigua, J. Tao, P. Bali, P. George et al., Cotreatment with histone deacetylase inhibitor LAQ824 enhances Apo2L/tumor necrosis factor-related apoptosis inducing ligandinduced death inducing signaling complex activity and apoptosis of human acute leukemia cells, Cancer Res, vol.64, pp.2580-2589, 2004.
DOI : 10.1158/0008-5472.can-03-2629

URL : http://cancerres.aacrjournals.org/content/64/7/2580.full.pdf

T. R. Singh, S. Shankar, and R. K. Srivastava, HDAC inhibitors enhance the apoptosis-inducing potential of TRAIL in breast carcinoma, Oncogene, vol.24, pp.4609-4632, 2005.

S. Shankar, T. R. Singh, T. E. Fandy, T. Luetrakul, D. D. Ross et al., Interactive effects of histone deacetylase inhibitors and TRAIL on apoptosis in human leukemia cells: involvement of both death receptor and mitochondrial pathways, Int J Mol Med, vol.16, pp.1125-1163, 2005.

G. Iacomino, M. C. Medici, and G. L. Russo, Valproic acid sensitizes K562 erythroleukemia cells to TRAIL/Apo2Linduced apoptosis, Anticancer Res, vol.28, pp.855-64, 2008.

S. Inoue, N. Harper, R. Walewska, M. J. Dyer, and G. M. Cohen, Enhanced Fas-associated death domain recruitment by histone deacetylase inhibitors is critical for the sensitization of chronic lymphocytic leukemia cells to TRAIL-induced apoptosis, Mol Cancer Ther, vol.8, pp.3088-97, 2009.

G. M. Matthews, A. Newbold, and R. W. Johnstone, Intrinsic and extrinsic apoptotic pathway signaling as determinants of histone deacetylase inhibitor antitumor activity, Adv Cancer Res, vol.116, pp.165-97, 2012.

Y. Lee, S. H. Kim, H. S. Kim, M. J. Son, H. Nakajima et al., Inhibition of hypoxia-induced angiogenesis by FK228, a specific histone deacetylase inhibitor, via suppression of HIF-1alpha activity, Biochem Biophys Res Commun, vol.300, pp.241-247, 2003.

H. Sawa, H. Murakami, Y. Ohshima, M. Murakami, I. Yamazaki et al., Histone deacetylase inhibitors such as sodium butyrate and trichostatin A inhibit vascular endothelial growth factor (VEGF) secretion from human glioblastoma cells, Brain Tumor Pathol, vol.19, pp.77-81, 2002.

Y. Sasakawa, Y. Naoe, T. Noto, T. Inoue, T. Sasakawa et al., Antitumor efficacy of FK228, a novel histone deacetylase inhibitor, depends on the effect on expression of angiogenesis factors, Biochem Pharmacol, vol.66, pp.897-906, 2003.

D. Zgouras, U. Becker, S. Loitsch, and J. Stein, Modulation of angiogenesis-related protein synthesis by valproic acid, Biochem, Biophys Res Commun, vol.316, pp.693-700, 2004.

U. Heider, M. Kaiser, J. Sterz, I. Zavrski, C. Jakob et al., Histone deacetylase inhibitors reduce VEGF production and induce growth suppression and apoptosis in human mantle cell lymphoma, Eur J Haematol, vol.76, pp.42-50, 2006.

M. S. Kim, H. J. Kwon, Y. M. Lee, and J. H. Baek,

K. W. Kim and . Kim, Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes, Nat Med, vol.7, pp.437-480, 2001.

D. Z. Qian, S. K. Kachhap, S. J. Collis, H. M. Verheul, M. A. Carducci et al., Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha, Cancer Res, vol.66, pp.8814-8835, 2006.

H. T. Cheng and W. C. Hung, Inhibition of proliferation, sprouting, tube formation and Tie2 signaling of lymphatic endothelial cells by the histone deacetylase inhibitor SAHA, Oncol Rep, vol.30, pp.961-968, 2013.

R. K. Srivastava, R. Kurzrock, and S. Shankar, MS-275 sensitizes TRAIL-resistant breast cancer cells, inhibits angiogenesis and metastasis, and reverses epithelial-mesenchymal transition in vivo, Mol Cancer Ther, vol.9, pp.3254-66, 2010.

A. Munshi, J. F. Kurland, T. Nishikawa, T. Tanaka, M. L. Hobbs et al., Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity, Clin Cancer Res, vol.11, pp.4912-4934, 2005.

C. S. Chen, Y. C. Wang, H. C. Yang, P. H. Huang, S. K. Kulp et al., Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku70 acetylation, Cancer Res, vol.67, pp.5318-5345, 2007.

Y. Zhang, T. Carr, A. Dimtchev, N. Zaer, A. Dritschilo et al., Attenuated DNA damage repair by trichostatin A through BRCA1 suppression, Radiat Res, vol.168, pp.115-139, 2007.

S. Adimoolam, M. Sirisawad, J. Chen, P. Thiemann, J. M. Ford et al., HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination, Proc Natl Acad Sci U A, vol.104, pp.19482-19489, 2007.

S. K. Kachhap, N. Rosmus, S. J. Collis, M. S. Kortenhorst, M. D. Wissing et al., Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor, PLoS One, vol.5, p.11208, 2010.

M. Koprinarova, P. Botev, and G. Russev, Histone deacetylase inhibitor sodium butyrate enhances cellular radiosensitivity by inhibiting both DNA nonhomologous end joining and homologous recombination, DNA Repair Amst, vol.10, pp.970-977, 2011.

J. H. Lee, M. L. Choy, L. Ngo, S. S. Foster, and P. A. Marks, Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair, Proc Natl Acad Sci U A, vol.107, pp.14639-14683, 2010.

R. R. Rosato, J. A. Almenara, and S. Grant, 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 1, Cancer Res, vol.63, pp.3637-3682, 2003.

C. Yu, M. Subler, M. Rahmani, E. Reese, G. Krystal et al., Induction of apoptosis in BCR/ABL+ cells by histone deacetylase inhibitors involves reciprocal effects on the RAF/MEK/ERK and JNK pathways, Cancer Biol Ther, vol.2, pp.544-51, 2003.

L. M. Butler, X. Zhou, W. S. Xu, H. I. Scher, R. A. Rifkind et al., The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxinbinding protein-2, and down-regulates thioredoxin, Proc Natl Acad Sci U A, vol.99, pp.11700-11705, 2002.

J. Ungerstedt, Y. Du, H. Zhang, D. Nair, and A. Holmgren, In vivo redox state of human thioredoxin and redox shift by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA), Free Radic Biol Med, vol.53, pp.2002-2009, 2012.

A. Mitra, L. Mishra, S. Li, and E. , CTCs and CSCs in tumor relapse and drug-resistance, Oncotarget, vol.6, pp.10697-711, 2015.

W. L. Tam and R. A. Weinberg, The epigenetics of epithelialmesenchymal plasticity in cancer, Nat Med, vol.19, pp.1438-1487, 2013.

F. Bruzzese, A. Leone, M. Rocco, C. Carbone, G. Piro et al., HDAC inhibitor vorinostat enhances the antitumor effect of gefitinib in squamous cell carcinoma of head and neck by modulating ErbB receptor expression and reverting EMT, J Cell Physiol, vol.226, pp.2378-90, 2011.

S. Mateen, K. Raina, C. Agarwal, D. Chan, and R. Agarwal, Silibinin synergizes with histone deacetylase and DNA methyltransferase inhibitors in upregulating E-cadherin expression together with inhibition of migration and invasion of human non-small cell lung cancer cells, J Pharmacol Exp Ther, vol.345, pp.320-326, 2013.

B. Chang, Y. Chen, Y. Zhao, and R. K. Bruick, JMJD6 Is a Histone Arginine Demethylase, Science, vol.318, p.444, 2007.

L. Hu, J. Lu, J. Cheng, Q. Rao, Z. Li et al., Structural insight into substrate preference for TET-mediated oxidation, Nature, vol.527, pp.118-122, 2015.

A. Bassan, M. R. Blomberg, T. Borowski, and P. E. , Siegbahn, Theoretical studies of enzyme mechanisms involving high-valent iron intermediates, High-Val. Iron Intermed, Biol, vol.100, pp.727-743, 2006.

J. C. Price, E. W. Barr, L. M. Hoffart, C. Krebs, and J. M. , Bollinger, Kinetic Dissection of the Catalytic Mechanism of Taurine:?-Ketoglutarate Dioxygenase (TauD) from Escherichia coli, Biochemistry (Mosc.), vol.44, pp.8138-8147, 2005.

P. K. Grzyska, E. H. Appelman, R. P. Hausinger, and D. A. Proshlyakov, Insight into the mechanism of an iron dioxygenase by resolution of steps following the Fe(IV)?O species, Proc. Natl. Acad. Sci. U. S. A, vol.107, pp.3982-3987, 2010.

T. Kouzarides, Chromatin Modifications and Their Function, Cell, vol.128, pp.693-705
DOI : 10.1016/j.cell.2007.02.005

URL : https://doi.org/10.1016/j.cell.2007.02.005

K. Fortschegger and R. Shiekhattar, Plant homeodomain fingers form a helping hand for transcription, Epigenetics, vol.6, pp.4-8, 2011.

S. Krishnan, S. Horowitz, and R. C. Trievel, Structure and Function of Histone H3 Lysine 9 Methyltransferases and Demethylases, ChemBioChem, vol.12, pp.254-263, 2011.

L. J. Walport, R. J. Hopkinson, and C. J. Schofield, Mechanisms of human histone and nucleic acid demethylases, Mech. Aesthetics? Mol. Imaging, vol.16, pp.525-534, 2012.

R. J. Klose, E. M. Kallin, and Y. Zhang, JmjC-domaincontaining proteins and histone demethylation, p.715, 2006.

R. J. Klose, E. M. Kallin, and Y. Zhang, JmjC-domaincontaining proteins and histone demethylation, Nat Rev Genet, issue.7, pp.715-727

L. J. Walport, R. J. Hopkinson, and C. J. Schofield, Mechanisms of human histone and nucleic acid demethylases, Curr Opin Chem Biol, vol.16, pp.525-534

Y. Tsukada, J. Fang, H. Erdjument-bromage, M. E. Warren, C. H. Borchers et al., Histone demethylation by a family of JmjC domain-containing proteins, Nat. Lond. U K, vol.439, pp.811-816

Y. Shi, Histone lysine demethylases: emerging roles in development, physiology and disease, Nat Rev Genet, vol.8, pp.829-833

I. Hoffmann, M. Roatsch, M. L. Schmitt, L. Carlino, M. Pippel et al., The role of histone demethylases in cancer therapy, Mol Oncol, issue.6, pp.683-703

J. W. Hojfeldt, K. Agger, and K. Helin, Histone lysine demethylases as targets for anticancer therapy, Nat Rev Drug Discov, vol.12

F. Crea, L. Sun, A. Mai, Y. T. Chiang, W. L. Farrar et al., The emerging role of histone lysine demethylases in prostate cancer, Mol Cancer, vol.11, p.52

A. Shmakova, M. Batie, J. Druker, and S. Rocha, Chromatin and oxygen sensing in the context of JmjC histone demethylases, Biochem J, vol.462

K. W. Wagner, H. Alam, S. S. Dhar, U. Giri, N. Li et al.,

B. Chan, B. Erez, J. Saigal, H. Chung, X. Lin et al., KDM2A promotes lung tumorigenesis by epigenetically enhancing ERK1/2 signaling, J Clin Invest, vol.123, pp.5231-5246

H. Liu, L. Liu, A. Holowatyj, Y. Jiang, and Z. Yang, Integrated genomic and functional analyses of histone demethylases identify oncogenic KDM2A isoform in breast cancer, Mol Carcinog, vol.55

Y. Huang, Y. Liu, L. Yu, J. Chen, J. Hou et al., Histone demethylase KDM2A promotes tumor cell growth and migration in gastric cancer, Tumor Biol, vol.36, pp.271-278

D. Frescas, D. Guardavaccaro, S. M. Kuchay, H. Kato, A. Poleshko et al., KDM2A represses transcription of centromeric satellite repeats and maintains the heterochromatic state, Cell Cycle, pp.3539-3547

D. Frescas, D. Guardavaccaro, F. Bassermann, R. Koyamanasu, and M. Pagano, JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes, Nat. Lond. U K, vol.450

J. He, A. T. Nguyen, and Y. Zhang, KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia, pp.3869-3880

A. Tzatsos, P. Paskaleva, F. Ferrari, V. Deshpande, S. Stoykova et al., KDM2B promotes pancreatic cancer via Polycomb-dependent and-independent transcriptional programs, J Clin Invest, vol.123

F. Kottakis, C. Polytarchou, P. Foltopoulou, I. Sanidas, S. C. Kampranis et al., FGF-2 Regulates Cell Proliferation, Migration, and Angiogenesis through an NDY1/KDM2B-miR-101-EZH2 Pathway, Mol Cell, vol.43, pp.285-298

M. A. Wade, D. Jones, L. Wilson, J. Stockley, K. Coffey et al., The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast

, Epigenetic Metalloenzymes Current Medicinal Chemistry, vol.25, issue.00, p.31, 2018.

, Nucleic Acids Res, vol.43, pp.196-207

J. Qi, K. Nakayama, R. D. Cardiff, A. D. Borowsky, K. Kaul et al., Siah2-dependent concerted activity of HIF and FoxA2 regulates formation of neuroendocrine phenotype and neuroendocrine prostate tumors, Cancer Cell, vol.18, pp.23-38

M. Uemura, H. Yamamoto, I. Takemasa, K. Mimori, H. Hemmi et al., Jumonji Domain Containing 1A Is a Novel Prognostic Marker for Colorectal Cancer: In vivo Identification from Hypoxic Tumor Cells, Clin Cancer Res, vol.16, pp.4636-4646

X. Guo, M. Shi, L. Sun, Y. Wang, Y. Gui et al., The expression of histone demethylase JMJD1A in renal cell carcinoma, Neoplasma, vol.58, pp.153-157

D. Yamada, S. Kobayashi, H. Yamamoto, Y. Tomimaru, T. Noda et al., Role of the hypoxia-related gene, JMJD1A, in hepatocellular carcinoma: clinical impact on recurrence after hepatic resection, Ann Surg Oncol, vol.19, issue.3, pp.355-64, 2012.

E. C. Kauffman, B. D. Robinson, M. J. Downes, L. G. Powell, M. M. Lee et al., Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer, Mol Carcinog, vol.50, pp.931-944

Q. Ye, A. Holowatyj, J. Wu, H. Liu, L. Zhang et al., Genetic alterations of KDM4 subfamily and therapeutic effect of novel demethylase inhibitor in breast cancer, Am J Cancer Res, vol.5, pp.1519-1530

J. G. Pryor, B. A. Brown-kipphut, A. Iqbal, and G. A. Scott, Microarray comparative genomic hybridization detection of copy number changes in desmoplastic melanoma and malignant peripheral nerve sheath tumor, Am J Dermatopathol, vol.33, pp.780-785, 2011.

G. Liu, A. Bollig-fischer, B. Kreike, M. J. Van-de-vijver, J. Abrams et al., Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer, Oncogene, vol.28

K. Uimonen, H. Merikallio, P. Paakko, T. Harju, A. Mannermaa et al., GASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma, Histol Histopathol, vol.29, pp.797-804, 2014.

Z. Q. Yang, I. Imoto, Y. Fukuda, A. Pimkhaokham, Y. Shimada et al., Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines, Cancer Res, vol.60, pp.4735-4744

L. Sun, J. Wu, Z. Wu, J. Shen, X. Xu et al., A three-gene signature and clinical outcome in esophageal squamous cell carcinoma, Int J Cancer, vol.136

Y. Ozaki, K. Fujiwara, M. Ikeda, T. Ozaki, T. Terui et al., The oncogenic role of GASC1 in chemically induced mouse skin cancer, Mamm Genome, vol.26, pp.591-597

H. E. Suikki, P. M. Kujala, T. L. Tammela, W. M. Van-weerden, R. L. Vessella et al., Genetic alterations and changes in expression of histone demethylases in prostate cancer, vol.70, pp.889-898

U. Vinatzer, M. Gollinger, L. Muellauer, M. Raderer, A. Chott et al., Mucosa-Associated Lymphoid Tissue Lymphoma: Novel Translocations Including Rearrangements of ODZ2, JMJD2C, and CNN3, vol.14, pp.6426-6431

A. Ehrbrecht, U. Mueller, M. Wolter, A. Hoischen, A. Koch et al., Comprehensive genomic analysis of desmoplastic medulloblastomas: identification of novel amplified genes and separate evaluation of the different histological components, J Pathol, vol.208

Y. Teng, C. Lee, Y. Li, Y. Chen, P. Hsiao et al.,

C. Jeng, Q. Hsu, M. Yan, L. Tsai, and . Juan, Histone Demethylase RBP2 Promotes Lung Tumorigenesis and Cancer Metastasis, Cancer Res, vol.73, pp.4711-4721

G. G. Wang, J. Song, Z. Wang, H. L. Dormann, F. Casadio et al., Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger, Nat. Lond. U K, vol.459, pp.847-851

T. Vogt, M. Kroiss, M. Mcclelland, C. Gruss, B. Becker et al., Deficiency of a novel retinoblastoma binding protein 2-homolog is a consistent feature of sporadic human melanoma skin cancer, Lab Invest, vol.79, pp.1615-1627

A. Roesch, B. Becker, S. Meyer, P. Wild, C. Hafner et al., Retinoblastoma-binding protein 2homolog 1: a retinoblastoma-binding protein downregulated in malignant melanomas, Mod Pathol, vol.18

S. Yamamoto, Z. Wu, H. G. Russnes, S. Takagi, G. Peluffo et al., JARID1B Is a Luminal Lineage-Driving Oncogene in Breast Cancer, Cancer Cell, vol.25, pp.762-777

Y. Xiang, Z. Zhu, G. Han, X. Ye, B. Xu et al., JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer, Proc Natl Acad Sci U A, vol.104

S. Hayami, J. D. Kelly, H. Cho, M. Yoshimatsu, M. Unoki et al., Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers, Int J Cancer, vol.128, pp.574-586

Z. Jangravi, M. S. Tabar, M. Mirzaei, P. Parsamatin, H. Vakilian et al., Two splice variants of Y chromosome-Located lysine-specific demethylase 5D have distinct function in prostate cancer Cell line (DU-145), J Proteome Res, vol.14, pp.3492-3502

J. Stein, M. Majores, M. Rohde, S. Lim, S. Schneider et al., KDM5C Is Overexpressed in Prostate Cancer and Is a Prognostic Marker for ProstateSpecific Antigen-Relapse Following Radical Prostatectomy, Am J Pathol, vol.184, pp.2430-2437

G. L. Dalgliesh, K. Furge, C. Greenman, L. Chen, G. Bignell et al.,

K. W. Kok, C. Lau, M. Leroy, D. J. Lin, M. Mcbride et al., Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes, Nat. Lond. U K, vol.463, pp.360-363

J. Liu, W. Lee, Z. Jiang, Z. Chen, S. Jhunjhunwala et al.,

J. Wu, F. J. Settleman, R. C. De-sauvage, R. M. Gentleman, D. Neve et al., Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events, Genome Res, vol.22, pp.2315-2327

E. Nakata, Y. Yukimachi, H. Kariyazono, S. Im, C. Abe et al., Design of a bioreductively-activated fluorescent pH probe for tumor hypoxia imaging, Bioorg Med Chem, vol.17, pp.6952-6958

G. Van-haaften, G. L. Dalgliesh, H. Davies, L. Chen, G. Bignell et al., Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer, Nat Genet, vol.41, pp.521-523

I. Ibragimova, M. E. Maradeo, E. Dulaimi, and P. Cairns, Aberrant promoter hypermethylation of PBRM1, BAP1, SETD2, KDM6A and other chromatin-modifying genes is absent or rare in clear cell RCC, pp.486-493

E. M. Smith, K. Boyd, and F. E. Davies, The potential role of epigenetic therapy in multiple myeloma, Br J Haematol, vol.148

Y. Gui, G. Guo, Y. Huang, X. Hu, A. Tang et al., Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder, Nat Genet, vol.43, pp.875-878

P. Ntziachristos, A. Tsirigos, G. G. Welstead, T. Trimarchi, S. Bakogianni et al.,

R. Kruidenier, S. Prinjha, P. Akira, A. A. Van-vlierberghe, R. Ferrando et al., Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia, Nat. Lond. U K, vol.514, pp.513-517

J. Kim, A. Sharma, S. S. Dhar, S. Lee, B. Gu et al., UTX and MLL4 Coordinately Regulate Transcriptional Programs for Cell Proliferation and Invasiveness in Breast Cancer Cells, Cancer Res, vol.74, pp.1705-1717

J. Ma, N. Wang, Y. Zhang, C. Wang, T. Ge et al., KDM6B Elicits Cell Apoptosis by Promoting Nuclear Translocation of FOXO1 in Non-Small Cell Lung Cancer, Cell Physiol Biochem, vol.37, pp.201-213

P. Zhang, X. Wang, W. Zhao, B. Qi, Q. Yang et al., DNA methylation-mediated repression of miR-941 enhances lysine (K)-specific demethylase 6B expression in hepatoma cells, J Biol Chem, vol.289

T. Y. Lin, Y. C. Cheng, H. C. Yang, W. C. Lin, C. C. Wang et al., Loss of the candidate tumor suppressor BTG3 triggers acute cellular senescence via the ERKJMJD3-p16INK4a signaling axis, pp.3287-3297

K. Komiya, N. Sueoka-aragane, A. Sato, T. Hisatomi, T. Sakuragi et al., Expression of Mina53, a novel c-Myc target gene, is a favorable prognostic marker in early stage lung cancer, Lung Cancer, vol.69, pp.232-240, 2010.

C. Suzuki, K. Takahashi, S. Hayama, N. Ishikawa, T. Kato et al., Identification of Myc-associated protein with JmjC domain as a novel therapeutic target oncogene for lung cancer, Mol Cancer Ther, issue.6, pp.542-551

E. K. Wagner, N. Nath, R. Flemming, J. B. Feltenberger, and J. M. Denu, Identification and Characterization of Small Molecule Inhibitors of a Plant Homeodomain Finger, Biochemistry (Mosc, pp.8293-8306

M. A. Mcdonough, C. Loenarz, R. Chowdhury, I. J. Clifton, and C. J. Schofield, Structural studies on human 2-oxoglutarate dependent oxygenases, Curr Opin Struct Biol, vol.20, pp.659-672

W. Aik, M. A. Mcdonough, A. Thalhammer, R. Chowdhury, and C. J. Schofield, Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenases, Catal. Regul. ? Proteins, vol.22, pp.691-700, 2012.

C. J. Schofield and P. J. Ratcliffe, Oxygen sensing by HIF hydroxylases, Nat Rev Mol Cell Biol, vol.5, pp.343-354
DOI : 10.1038/nrm1366

N. R. Rose, M. A. Mcdonough, O. N. King, A. Kawamura, and C. J. Schofield, Inhibition of 2-oxoglutarate dependent oxygenases, Chem Soc Rev, vol.40, pp.4364-4397
DOI : 10.1039/c0cs00203h

C. J. Cunliffe, T. J. Franklin, N. J. Hales, and G. B. Hill, Novel inhibitors of prolyl 4-hydroxylase. 3. Inhibition by the substrate analog N-oxaloglycine and its derivatives, J Med Chem, vol.35

G. Opocher and F. Schiavi, Functional consequences of succinate dehydrogenase mutations, Endocr Pr, vol.17, issue.3, pp.64-71, 2011.
DOI : 10.4158/ep11070.ra

L. Dang, D. W. White, S. Gross, B. D. Bennett, M. A. Bittinger et al.,

, Epigenetic Metalloenzymes Current Medicinal Chemistry, vol.25, issue.00, p.33, 2018.

K. M. Keenan, R. M. Marks, P. S. Prins, K. E. Ward, L. M. Yen et al., Cancer-associated IDH1 mutations produce 2-hydroxyglutarate, Nat. Lond. U K, vol.462

J. Losman, R. E. Looper, P. Koivunen, S. Lee, R. K. Schneider et al., (R)-2-Hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible, Sci. Wash. DC U S, vol.339
DOI : 10.1126/science.1231677

URL : http://europepmc.org/articles/pmc3836459?pdf=render

U. Puistola, T. M. Turpeenniemi-hujanen, R. Myllyla, and K. I. Kivirikko, Studies on the lysyl hydroxylase reaction. I. Initial velocity kinetics and related aspects, vol.611, pp.90040-90046

R. Myllyla, L. Tuderman, and K. I. Kivirikko, Mechanism of the prolyl hydroxylase reaction. 2. Kinetic analysis of the reaction sequence, Eur J Biochem, vol.80, pp.349-57

M. Xiao, H. Yang, W. Xu, S. Ma, H. Lin et al.,

. Guan, Inhibition of ?-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors, Genes Dev, vol.26, pp.1326-1338

N. R. Rose, S. S. Ng, J. Mecinovic, B. M. Lienard, S. H. Bello et al., Inhibitor Scaffolds for 2-OxoglutarateDependent Histone Lysine Demethylases, J Med Chem, vol.51, pp.7053-7056
DOI : 10.1021/jm800936s

J. Couture, E. Collazo, P. A. Ortiz-tello, J. S. Brunzelle, and R. C. Trievel, Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase, Nat Struct Mol Biol, vol.14, pp.689-695

E. D. Mackenzie, M. A. Selak, D. A. Tennant, L. J. Payne, S. Crosby et al., Cellpermeating ?-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells, Mol Cell Biol, vol.27, pp.3282-3289

S. Hamada, T. Suzuki, K. Mino, K. Koseki, F. Oehme et al., Design, Synthesis, EnzymeInhibitory Activity, and Effect on Human Cancer Cells of a Novel Series of Jumonji Domain-Containing Protein 2 Histone Demethylase Inhibitors, J Med Chem, vol.53, pp.5629-5638

T. Suzuki, H. Ozasa, Y. Itoh, P. Zhan, H. Sawada et al.,

, Histone Lysine Demethylase Subfamily Inhibitor and its Antiproliferative Activity, J Med Chem, vol.56

N. R. Rose, E. C. Woon, A. Tumber, L. J. Walport, R. Chowdhury et al., Plant Growth Regulator Daminozide Is a Selective Inhibitor of Human KDM2/7 Histone Demethylases, J Med Chem, vol.55, pp.6639-6643

X. Luo, Y. Liu, S. Kubicek, J. Myllyharju, A. Tumber et al., A Selective Inhibitor and Probe of the Cellular Functions of Jumonji C DomainContaining Histone Demethylases, J Am Chem Soc, vol.133, pp.9451-9456

Y. Itoh, H. Sawada, M. Suzuki, T. Tojo, R. Sasaki et al., Identification of Jumonji AT-Rich Interactive Domain 1A Inhibitors and Their Effect on Cancer Cells, ACS Med Chem Lett, vol.6

O. N. King, X. S. Li, M. Sakurai, A. Kawamura, N. R. Rose et al., Quantitative high-throughput screening identifies 8hydroxyquinolines as cell-active histone demethylase inhibitors, PLoS One, vol.5

R. J. Hopkinson, A. Tumber, C. Yapp, R. Chowdhury, W. Aik et al., 5Carboxy-8-hydroxyquinoline is a broad spectrum 2oxoglutarate oxygenase inhibitor which causes iron translocation, Chem Sci, vol.4, pp.3110-3117

C. C. Thinnes, K. S. England, A. Kawamura, R. Chowdhury, C. J. Schofield et al., Targeting histone lysine demethylases-Progress, challenges, and the future, Methylation Multifaceted Modif.-Look. Transcr. Beyond, vol.1839, pp.1416-1432, 2014.

M. M. Mackeen, H. B. Kramer, K. Chang, M. L. Coleman, R. J. Hopkinson et al., SmallMolecule-Based Inhibition of Histone Demethylation in Cells Assessed by Quantitative Mass Spectrometry, J Proteome Res, issue.9

A. Thalhammer, J. Mecinovic, C. Loenarz, A. Tumber, N. R. Rose et al., Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates, Org Biomol Chem, vol.9, pp.127-135

L. Wang, J. Chang, D. Varghese, M. Dellinger, S. Kumar et al., A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth, Nat Commun, vol.4, p.2035, 2013.

T. E. Mcallister, K. S. England, R. J. Hopkinson, P. E. Brennan, A. Kawamura et al., Recent Progress in Histone Demethylase Inhibitors, J Med Chem, vol.59, pp.1308-1337, 2016.

K. Chang, O. N. King, A. Tumber, E. C. Woon, T. D. Heightman et al., Inhibition of Histone Demethylases by 4-Carboxy-2,2'Bipyridyl Compounds

R. W. Welford, I. Schlemminger, L. A. Mcneill, K. S. Hewitson, and C. J. Schofield, The Selectivity and Inhibition of AlkB, J Biol Chem, vol.278, pp.10157-10161

J. C. Murray, R. H. Cassell, and S. R. Pinnell, Inhibition of lysyl hydroxylase by catechol analogs, Biochim Biophys Acta Enzym, vol.481, pp.90137-90138

W. J. Wilson and L. Poellinger, The dietary flavonoid quercetin modulates HIF-1? activity in endothelial cells, Biochem Biophys Res Commun, vol.293

Y. Zhou, Y. Kim, X. Li, S. R. Baerson, A. K. Agarwal et al., HypoxiaInducible Factor-1 Activation by (-)-Epicatechin Gallate: Potential Adverse Effects of Cancer Chemoprevention with High-Dose Green Tea Extracts, J Nat Prod, vol.67, pp.2063-2069

M. Sakurai, N. R. Rose, L. Schultz, A. M. Quinn, A. Jadhav et al., A miniaturized screen for inhibitors of Jumonji histone demethylases, Mol BioSyst, vol.6, pp.357-364

A. L. Nielsen, L. H. Kristensen, K. B. Stephansen, J. B. Kristensen, C. Helgstrand et al., Identification of catechols as histonelysine demethylase inhibitors, FEBS Lett, vol.586, pp.1190-1194

L. Kruidenier, C. Chung, Z. Cheng, J. Liddle, K. H. Che et al., A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response, Nat. Lond. U K, vol.488, pp.404-408

C. C. Thinnes, K. S. England, A. Kawamura, R. Chowdhury, C. J. Schofield et al., Targeting histone lysine demethylases-Progress, challenges, and the future, Biochim Biophys Acta Gene Regul Mech, vol.1839, pp.1416-1432

M. Wissmann, N. Yin, J. M. Mueller, H. Greschik, B. D. Fodor et al., Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptordependent gene expression, Nat Cell Biol, issue.9

D. Rotili, S. Tomassi, M. Conte, R. Benedetti, M. Tortorici et al., Pan-Histone Demethylase Inhibitors Simultaneously Targeting Jumonji C and Lysine-Specific Demethylases Display High Anticancer Activities, J Med Chem, vol.57, pp.42-55

H. Zhao and T. Chen, Tet family of 5-methylcytosine dioxygenases in mammalian development, J. Hum. Genet, vol.58, p.421, 2013.

W. A. Pastor, L. Aravind, and A. Rao, TETonic shift: biological roles of TET proteins in DNA demethylation and transcription, Nat. Rev. Mol. Cell Biol, vol.14, pp.341-356, 2013.

M. R. Branco, G. Ficz, and W. Reik, Uncovering the role of 5hydroxymethylcytosine in the epigenome, Nat. Rev. Genet, vol.13, pp.7-13, 2011.

S. R. Kinney and S. Pradhan, Ten eleven translocation enzymes and 5-hydroxymethylation in mammalian development and cancer, Adv. Exp. Med. Biol, vol.754, pp.57-79, 2013.

S. Guibert and M. Weber, Functions of DNA methylation and hydroxymethylation in mammalian development, Curr. Top. Dev. Biol, vol.104, pp.47-83, 2013.

K. D. Rasmussen and K. Helin, Role of TET enzymes in DNA methylation, development, and cancer, Genes Dev, vol.30, pp.733-750, 2016.

M. M. Dawlaty, A. Breiling, T. Le, M. I. Barrasa, G. Raddatz et al., Loss of Tet enzymes compromises proper differentiation of embryonic stem cells, Dev. Cell, vol.29, pp.102-111, 2014.

Y. Gao, J. Chen, K. Li, T. Wu, B. Huang et al., Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming, Cell Stem Cell, vol.12, pp.453-469, 2013.

K. Williams, J. Christensen, and K. Helin, DNA methylation: TET proteins-guardians of CpG islands?, EMBO Rep, vol.13, pp.28-35, 2011.

J. Ma, T. Zhang, W. Shen, H. Schatten, and Q. Y. Sun, Molecules and mechanisms controlling the active DNA demethylation of the mammalian zygotic genome, Protein Cell, vol.5, pp.827-836, 2014.

L. Scourzic, E. Mouly, and O. A. Bernard, TET proteins and the control of cytosine demethylation in cancer, Genome Med, vol.7, p.9, 2015.

T. F. Kraus, A. Greiner, M. Steinmaurer, V. Dietinger, V. Guibourt et al., Genetic Characterization of Ten-Eleven-Translocation Methylcytosine Dioxygenase Alterations in Human Glioma, J. Cancer, vol.6, pp.832-842, 2015.

S. Bassi, T. Tripathi, A. Monziani, F. Di-leva, and M. Biagioli, Epigenetics of Huntington's Disease, vol.978, pp.277-299, 2017.

R. Lardenoije, A. Iatrou, G. Kenis, K. Kompotis, H. W. Steinbusch et al., The epigenetics of aging and neurodegeneration, Prog. Neurobiol, vol.131, pp.21-64, 2015.

S. Al-mahdawi, S. A. Virmouni, and M. A. Pook, The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases, Front. Neurosci, vol.8, p.397, 2014.

M. A. Bradley-whitman and M. A. Lovell, Epigenetic changes in the progression of Alzheimer's disease, Mech. Ageing Dev, vol.134, pp.486-495, 2013.

N. Coppieters, B. V. Dieriks, C. Lill, R. L. Faull, M. A. Curtis et al., Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain, Neurobiol. Aging, vol.35, pp.1334-1344, 2014.

F. Wang, Y. Yang, X. Lin, J. Wang, Y. Wu et al.,

C. Luo, C. Guo, T. Han, and . Tang, Genome-wide loss of 5hmC is a novel epigenetic feature of Huntington's disease, Hum. Mol. Genet, vol.22, pp.3641-3653, 2013.

X. Xu, X. Tan, B. Tampe, G. Nyamsuren, X. Liu et al., Epigenetic balance of aberrant Rasal1 promoter methylation and hydroxymethylation regulates cardiac fibrosis, Cardiovasc. Res, vol.105, pp.279-291, 2015.

A. H. Cull, B. Snetsinger, R. Buckstein, R. A. Wells, and M. J. Rauh, Tet2 restrains inflammatory gene expression in macrophages, Exp. Hematol, vol.55, 2017.

J. Peng, Z. Tang, Z. Ren, B. He, Y. Zeng et al., TET2 Protects against oxLDL-Induced HUVEC Dysfunction by Upregulating the CSE/H2S System, vol.8, p.486, 2017.

L. Bird, Inflammation: TET2: the terminator, Nat. Rev. Immunol, vol.15, p.598, 2015.

A. Greißel, M. Culmes, R. Napieralski, E. Wagner, H. Gebhard et al., Alternation of histone and DNA methylation in human atherosclerotic carotid plaques, Thromb. Haemost, vol.114, pp.390-402, 2015.

P. Fagone, K. Mangano, R. D. Marco, C. Touil-boukoffa, T. Chikovan et al., Expression of DNA methylation genes in secondary progressive multiple sclerosis, J. Neuroimmunol, vol.290, pp.66-69, 2016.

E. A. Abdel-hameed, H. Ji, and M. T. Shata, HIV-Induced Epigenetic Alterations in Host Cells, Adv. Exp. Med. Biol, vol.879, pp.27-38, 2016.

B. Delatte, R. Deplus, and F. Fuks, Playing TETris with DNA modifications, EMBO J, vol.33, pp.1198-1211, 2014.

S. Liu, J. Jiang, L. Li, N. J. Amato, Z. Wang et al., Arsenite Targets the Zinc Finger Domains of Tet Proteins and Inhibits Tet-Mediated Oxidation of 5-Methylcytosine, Environ, Sci. Technol, vol.49, pp.11923-11931, 2015.

L. E. Alves, E. P. Rose, and T. B. Cahill, Intravenous amiodarone in the treatment of refractory arrhythmias, Crit. Care Med, vol.13, pp.750-752, 1985.

Y. Costa, J. Ding, T. W. Theunissen, F. Faiola, T. A. Hore et al., NANOG-dependent function of TET1 and TET2 in establishment of pluripotency, Nature, vol.495, pp.370-374, 2013.

Y. Wang, M. Xiao, X. Chen, L. Chen, Y. Xu et al., WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation, Mol. Cell, vol.57, pp.662-673, 2015.

P. Cartron, A. Nadaradjane, F. Lepape, L. Lalier, B. Gardie et al., Identification of TET1 Partners That Control Its DNA-Demethylating Function, Genes Cancer, vol.4, pp.235-241, 2013.

M. Cheray, R. Pacaud, A. Nadaradjane, L. Oliver, F. M. Vallette et al., Specific Inhibition of DNMT3A/ISGF3? Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth, Theranostics, vol.6, pp.1988-1999, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-01414173

M. Cheray, R. Pacaud, A. Nadaradjane, F. M. Vallette, and P. Cartron, Specific inhibition of one DNMT1-including complex influences tumor initiation and progression, Clin. Epigenetics, vol.5, p.9, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-00851207

M. Cheray, A. Nadaradjane, P. Bonnet, S. Routier, F. M. Vallette et al., Specific inhibition of DNMT1/CFP1 reduces cancer phenotypes and enhances chemotherapy effectiveness, Epigenomics, vol.6, pp.267-275, 2014.

G. Ferrari-amorotti, V. Fragliasso, R. Esteki, Z. Prudente, A. R. Soliera et al., Inhibiting interactions of lysine demethylase LSD1 with snail/slug blocks cancer cell invasion, Cancer Res, vol.73, pp.235-245, 2013.

R. Plummer, L. Vidal, M. Griffin, M. Lesley, J. De-bono et al., Phase I study of MG98, an oligonucleotide antisense inhibitor of human DNA methyltransferase 1, given as a 7-day infusion in patients with advanced solid tumors, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.15, pp.3177-3183, 2009.

H. Yamamoto and P. V. Mohanan, Effect of alpha-ketoglutarate and oxaloacetate on brain mitochondrial DNA damage and seizures induced by kainic acid in mice, Toxicol. Lett, vol.143, pp.115-122, 2003.

W. Xu, H. Yang, Y. Liu, Y. Yang, P. Wang et al.,

S. Guan, Y. Zhao, and . Xiong, Oncometabolite 2hydroxyglutarate is a competitive inhibitor of ?ketoglutarate-dependent dioxygenases, Cancer Cell, vol.19, 2011.

M. Xiao, H. Yang, W. Xu, S. Ma, H. Lin et al.,

. Guan, Inhibition of ?-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors, Genes Dev, vol.26, pp.1326-1338, 2012.

M. Ko, J. An, H. S. Bandukwala, L. Chavez, T. Aijö et al., Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX, Nature, vol.497, pp.122-126, 2013.

L. Cimmino, I. Dolgalev, Y. Wang, A. Yoshimi, G. H. Martin et al., Neel, I. Aifantis, Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression, Cell, vol.170, pp.1079-1095, 2017.

N. Martinet and P. Bertrand, Interpreting clinical assays for histone deacetylase inhibitors, Cancer Manag Res, vol.3, pp.117-158, 2011.

H. Maeda, Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity, Adv. Drug Deliv. Rev, 2015.

T. M. Allen and F. J. Martin, Advantages of liposomal delivery systems for anthracyclines, Semin Oncol, vol.31, pp.5-15, 2004.

A. Gabizon, H. Shmeeda, and Y. Barenholz, Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies, Clin Pharmacokinet, vol.42, pp.419-455, 2003.

F. Bahhaj, F. J. Dekker, N. Martinet, and P. Bertrand, Delivery of epidrugs, Drug Discov. Today, vol.19, pp.1337-1352, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01201998

R. Delatouche, I. Denis, M. Grinda, F. E. Bahhaj, E. Baucher et al., Design of pH responsive clickable prodrugs applied to histone deacetylase inhibitors: A new strategy for anticancer therapy, Eur. J. Pharm. Biopharm, vol.85, pp.862-872, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01006764

F. Gueugnon, I. Denis, D. Pouliquen, F. Collette, R. Delatouche et al., Blanquart, Nanoparticles produced by ring-opening metathesis polymerization using norbornenyl-poly(ethylene oxide) as a ligand-free generic platform for highly selective in vivo tumor targeting, Biomacromolecules, vol.14, pp.2396-402, 2013.

C. Charrier, J. Clarhaut, J. Gesson, G. Estiu, O. Wiest et al., Synthesis and Modeling of New Benzofuranone Histone Deacetylase Inhibitors that Stimulate Tumor Suppressor Gene Expression, J. Med. Chem, vol.52, pp.3112-3115, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00438795

F. E. Bahhaj, I. Denis, L. Pichavant, R. Delatouche, F. Collette et al.,

P. Blanquart and . Bertrand, Histone Deacetylase Inhibitors Delivery using Nanoparticles with Intrinsic Passive Tumor Targeting Properties for Tumor Therapy, Theranostics, vol.6, pp.795-807, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-01299450

S. B. Baylin and P. A. Jones, A decade of exploring the cancer epigenome-biological and translational implications, Nat Rev Cancer, vol.11, pp.726-760, 2011.

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