The SUV39H1 inhibitor chaetocin induces differentiation and shows synergistic cytotoxicity with other epigenetic drugs in acute myeloid leukemia cells

Blood Cancer Journal

Volumn 5, Issue 5, 2015, Pages

  Lai, Y S ^a   Chen, J Y ^a   Tsai, H J ^a,b   Chen, T Y ^b   Hung, W C ^a,c  

^a NATIONAL HEALTH RESEARCH INSTITUTES   (Taiwan)

^b NATIONAL CHENG KUNG UNIVERSITY HOSPITAL   (Taiwan)

^c NATIONAL CHENG KUNG UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

2 CYCLOHEXYL N (1 ISOPROPYL 4 PIPERIDINYL) 6 METHOXY 7 [3 (1 PYRROLIDINYL)PROPOXY] 4 QUINAZOLINAMINE; 4 (4 CHLOROPHENYL) 2,3,9 TRIMETHYL 6H THIENO[3,2 F][1,2,4]TRIAZOLO[4,3 A][1,4]DIAZEPINE 6 ACETIC ACID TERT BUTYL ESTER; ANTINEOPLASTIC AGENT; CD11B ANTIGEN; CHAETOCIN; METHYLTRANSFERASE; METHYLTRANSFERASE G9A; METHYLTRANSFERASE SUV39H1; METHYLTRANSFERASE SUV39H1 INHIBITOR; UNCLASSIFIED DRUG; VORINOSTAT; PIPERAZINE DERIVATIVE; REPRESSOR PROTEIN; SUV39H1 PROTEIN, HUMAN;

ACUTE MYELOBLASTIC LEUKEMIA; ANTIGEN EXPRESSION; ARTICLE; CANCER CELL LINE; CELL DEATH; CELL DIFFERENTIATION; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG POTENTIATION; EPIGENETICS; HL 60 CELL LINE; HUMAN; HUMAN CELL; KG 1A CELL LINE; TUMOR SUPPRESSOR GENE; U937 CELL LINE; ANTAGONISTS AND INHIBITORS; CELL CULTURE; DNA METHYLATION; DRUG EFFECTS; GENETIC EPIGENESIS; IMMUNOBLOTTING; LEUKEMIA, MYELOID, ACUTE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL DIFFERENTIATION; CELLS, CULTURED; DNA METHYLATION; DRUG SYNERGISM; EPIGENESIS, GENETIC; HUMANS; IMMUNOBLOTTING; LEUKEMIA, MYELOID, ACUTE; METHYLTRANSFERASES; PIPERAZINES; REPRESSOR PROTEINS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 84989315935     PISSN: None     EISSN: 20445385     Source Type: Journal    
DOI: 10.1038/bcj.2015.37     Document Type: Article

References (33)

1. Peter Chung YR, Schatoff E, Abdel-Wahab O. Epigenetic alterations in hematopoietic malignancies. Int J Hematol 2012; 96: 413-427.
2. Lehmann U, Brakensiek K, Kreipe H. Role of epigenetic changes in hematological malignancies. Ann Hematol 2004; 83: 137-152.
3. Jones PA. At the tipping point for epigenetic therapies in cancer. J Clin Invest 2014; 124: 14-16.
4. Mair B, Kubicek S, Nijman SM. Exploiting epigenetic vulnerabilities for cancer therapeutics. Trends Pharmacol Sci 2014; 35: 136-145.
5. Boros J, Arnoult N, Stroobant V, Collet JF, Decottignies A. Polycomb repressive complex 2 and H3K27me3 cooperate with H3K9 methylation to maintain heterochromatin protein 1alpha at chromatin. Mol Cell Biol 2014; 34: 3662-3674.
6. Towbin BD, Gonzalez-Aguilera C, Sack R, Gaidatzis D, Kalck V, Meister P et al. Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell 2012; 150: 934-947.
7. Li F, Huarte M, Zaratiegui M, Vaughn MW, Shi Y, Martienssen R et al. Lid2 is required for coordinating H3K4 and H3K9 methylation of heterochromatin and euchromatin. Cell 2008; 135: 272-283.
8. Stancheva I. Caught in conspiracy: Cooperation between DNA methylation and histone H3K9 methylation in the establishment and maintenance of heterochromatin. Biochem Cell Biol 2005; 83: 385-395.
9. Shinkai Y, Tachibana M. H3K9 methyltransferase G9a and the related molecule GLP. Genes Dev 2011; 25: 781-788.
10. Shankar SR, Bahirvani AG, Rao VK, Bharathy N, Ow JR, Taneja R. G9a, a multipotent regulator of gene expression. Epigenetics 2013; 8: 16-22.
11. Dong C, Wu Y, Yao J, Wang Y, Yu Y, Rychahou PG et al. G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer. J Clin Invest 2012; 122: 1469-1486.
12. Chen MW, Hua KT, Kao HJ, Chi CC, Wei LH, Johansson G et al. H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. Cancer Res 2010; 70: 7830-7840.
13. Purcell DJ, Khalid O, Ou CY, Little GH, Frenkel B, Baniwal SK et al. Recruitment of coregulator G9a by Runx2 for selective enhancement or suppression of transcription. J Cell Biochem 2012; 113: 2406-2414.
14. Lehnertz B, Pabst C, Su L, Miller M, Liu F, Yi L et al. The methyltransferase G9a regulates HoxA9-dependent transcription in AML. Genes Dev 2014; 28: 317-327.
15. Kubicek S, O'Sullivan RJ, August EM, Hickey ER, Zhang Q, Teodoro ML et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 2007; 25: 473-481.
16. Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V et al. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol 2011; 7: 566-574.
17. Fuks F, Hurd PJ, Deplus R, Kouzarides T. The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res 2003; 31: 2305-2312.
18. Chakraborty S, Sinha KK, Senyuk V, Nucifora G. SUV39H1 interacts with AML1 and abrogates AML1 transactivity. AML1 is methylated in vivo. Oncogene 2003; 22: 5229-5237.
19. Reed-Inderbitzin E, Moreno-Miralles I, Vanden-Eynden SK, Xie J, Lutterbach B, Durst-Goodwin KL et al. RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription. Oncogene 2006; 25: 5777-5786.
20. Goyama S, Nitta E, Yoshino T, Kako S, Watanabe-Okochi N, Shimabe M et al. EVI-1 interacts with histone methyltransferases SUV39H1 and G9a for transcriptional repression and bone marrow immortalization. Leukemia 2010; 24: 81-88.
21. Greiner D, Bonaldi T, Eskeland R, Roemer E, Imhof A. Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9. Nat Chem Biol 2005; 1: 143-145.
22. Cherblanc FL, Chapman KL, Reid J, Borg AJ, Sundriyal S, Alcazar-Fuoli L et al. On the histone lysine methyltransferase activity of fungal metabolite chaetocin. J Med Chem 2013; 56: 8616-8625.
23. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O et al. Selective inhibition of BET bromodomains. Nature 2010; 468: 1067-1073.
24. Lakshmikuttyamma A, Scott SA, DeCoteau JF, Geyer CR. Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition. Oncogene 2010; 29: 576-588.
25. Chaib H, Nebbioso A, Prebet T, Castellano R, Garbit S, Restouin A et al. Antileukemia activity of chaetocin via death receptor-dependent apoptosis and dual modulation of the histone methyl-Transferase SUV39H1. Leukemia 2012; 26: 662-674.
26. Teng Y, Iuchi K, Iwasa E, Fujishiro S, Hamashima Y, Dodo K et al. Unnatural enantiomer of chaetocin shows strong apoptosis-inducing activity through caspase-8/caspase-3 activation. Bioorg Med Chem Lett 2010; 20: 5085-5088.
27. Lee MC, Kuo YY, Chou WC, Hou HA, Hsiao M, Tien HF. Gfi-1 is the transcriptional repressor of SOCS1 in acute myeloid leukemia cells. J Leukoc Biol 2014; 95: 105-115.
28. Tran HT, Kim HN, Lee IK, Nguyen-Pham TN, Ahn JS, Kim YK et al. Improved therapeutic effect against leukemia by a combination of the histone methyltransferase inhibitor chaetocin and the histone deacetylase inhibitor trichostatin A. J Korean Med Sci 2013; 28: 237-246.
29. Song X, Zhao Z, Qi X, Tang S, Wang Q, Zhu T et al. Identification of epipolythiodioxopiperazines HDN-1 and chaetocin as novel inhibitor of heat shock protein 90. Oncotarget 2015; 6: 5263-5274.
30. Herrmann H, Blatt K, Shi J, Gleixner KV, Cerny-Reiterer S, Mullauer L et al. Small-molecule inhibition of BRD4 as a new potent approach to eliminate leukemic stem-And progenitor cells in acute myeloid leukemia AML. Oncotarget 2012; 3: 1588-1599.
31. Fiskus W, Sharma S, Qi J, Shah B, Devaraj SG, Leveque C et al. BET protein antagonist JQ1 is synergistically lethal with FLT3 tyrosine kinase inhibitor (TKI) and overcomes resistance to FLT3-TKI in AML cells expressing FLT-ITD. Mol Cancer Ther 2014; 13: 2315-2327.
32. Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci USA 2011; 108: 16669-16674.
33. Fowler T, Ghatak P, Price DH, Conaway R, Conaway J, Chiang CM et al. Regulation of MYC expression and differential JQ1 sensitivity in cancer cells. PLoS One 2014; 9: E87003.