A SIRT2-Selective Inhibitor Promotes c-Myc Oncoprotein Degradation and Exhibits Broad Anticancer Activity

Cancer Cell

Volumn 29, Issue 3, 2016, Pages 297-310

  Jing, Hui ^a   Hu, Jing ^a   He, Bin ^a   Negrón Abril, Yashira L ^a   Stupinski, Jack ^a   Weiser, Keren ^b   Carbonaro, Marisa ^b   Chiang, Ying Ling ^a   Southard, Teresa ^a   Giannakakou, Paraszkevi ^b,c   Weiss, Robert S ^a,c   Lin, Hening ^a,c  

^a Cornell University ^*  (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c GUIZHOU MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; LYSINE DERIVATIVE; MYC PROTEIN; ONCOPROTEIN; SIRTUIN 2; THIOMYRISTOYLLYSINE DERIVATIVE; UNCLASSIFIED DRUG; LYSINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER INHIBITION; CONTROLLED STUDY; DRUG POTENCY; DRUG SELECTIVITY; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN TARGETING; UBIQUITINATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BREAST TUMOR; CELL PROLIFERATION; DRUG EFFECTS; FEMALE; HELA CELL LINE; MCF-7 CELL LINE; METABOLISM; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; FEMALE; HELA CELLS; HUMANS; LYSINE; MCF-7 CELLS; MICE; ONCOGENE PROTEINS; PROTEOLYSIS; PROTO-ONCOGENE PROTEINS C-MYC; SIRTUIN 2; UBIQUITINATION;

EID: 84962920604     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccell.2016.02.007     Document Type: Article

References (57)

1. Bartek J., Mistrik M., Bartkova J. Thresholds of replication stress signaling in cancer development and treatment. Nat. Struct. Mol. Biol. 2012, 19:5-7.
2. Beroukhim R., Mermel C.H., Porter D., Wei G., Raychaudhuri S., Donovan J., Barretina J., Boehm J.S., Dobson J., Urashima M., et al. The landscape of somatic copy-number alteration across human cancers. Nature 2010, 463:899-905.
3. Chappell S.A., LeQuesne J.P., Paulin F.E., deSchoolmeester M.L., Stoneley M., Soutar R.L., Ralston S.H., Helfrich M.H., Willis A.E. A mutation in the c-myc-IRES leads to enhanced internal ribosome entry in multiple myeloma: a novel mechanism of oncogene de-regulation. Oncogene 2000, 19:4437-4440.
4. Chen J., Chan A.W., To K.F., Chen W., Zhang Z., Ren J., Song C., Cheung Y.S., Lai P.B., Cheng S.H., et al. SIRT2 overexpression in hepatocellular carcinoma mediates epithelial to mesenchymal transition by protein kinase B/glycogen synthase kinase-3beta/beta-catenin signaling. Hepatology 2013, 57:2287-2298.
5. Cheon M.G., Kim W., Choi M., Kim J.E. AK-1, a specific SIRT2 inhibitor, induces cell cycle arrest by downregulating Snail in HCT116 human colon carcinoma cells. Cancer Lett. 2015, 356:637-645.
6. Choi S.H., Wright J.B., Gerber S.A., Cole M.D. Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells. Genes Dev. 2010, 24:1236-1241.
7. Delmore J.E., Issa G.C., Lemieux M.E., Rahl P.B., Shi J., Jacobs H.M., Kastritis E., Gilpatrick T., Paranal R.M., Qi J., et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011, 146:904-917.
8. Di Fruscia P., Ho K.K., Laohasinnarong S., Khongkow M., Kroll S.H., Islam S.A., Sternberg M.J., Schmidtkunz K., Jung M., Lam E.W., Fuchter M.J. The discovery of novel 10,11-dihydro-5H-dibenz[b,f]azepine SIRT2 inhibitors. Medchemcomm 2012, 10.1039/C2MD00290F.
9. Du J., Zhou Y., Su X., Yu J., Khan S.H., Kim J., Woo J., Kim J.H., Choi B.H., et al. Sirt5 is an NAD-dependent protein lysine demalonylase and desuccinylase. Science 2011, 334:806-809.
10. Fang Y., Nicholl M.B. Sirtuin 1 in malignant transformation: friend or foe?. Cancer Lett. 2011, 306:10-14.
11. Fatkins D.G., Monnot A.D., Zheng W. Ne-Thioacetyl-lysine: a multi-facet functional probe for enzymatic protein lysine Ne-deacetylation. Bioorg. Med. Chem. Lett. 2006, 16:3651-3656.
12. Feldman J.L., Baeza J., Denu J.M. Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J. Biol. Chem. 2013, 288:31350-31356.
13. Guy C.T., Cardiff R.D., Muller W.J. Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol. Cell Biol. 1992, 12:954-961.
14. Haigis M.C., Sinclair D.A. Mammalian sirtuins: biological insights and disease relevance. Annu. Rev. Pathol. 2010, 5:253-295.
15. Hawse W.F., Hoff K.G., Fatkins D.G., Daines A., Zubkova O.V., Schramm V.L., Zheng W., Wolberger C. Structural insights into intermediate steps in the Sir2 deacetylation reaction. Structure 2008, 16:1368-1377.
16. He B., Du J., Lin H. Thiosuccinyl peptides as Sirt5-specific inhibitors. J. Am. Chem. Soc. 2012, 134:1922-1925.
17. He B., Hu J., Zhang X., Lin H. Thiomyristoyl peptides as cell-permeable Sirt6 inhibitors. Org. Biomol. Chem. 2014, 12:7498-7502.
18. Heltweg B., Gatbonton T., Schuler A.D., Posakony J., Li H., Goehle S., Kollipara R., Depinho R.A., Gu Y., Simon J.A., Bedalov A. Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006, 66:4368-4377.
19. Herranz D., Serrano M. SIRT1: recent lessons from mouse models. Nat. Rev. Cancer 2010, 10:819-823.
20. Hoffmann G., Breitenbucher F., Schuler M., Ehrenhofer-Murray A.E. A novel sirtuin 2 (SIRT2) inhibitor with p53-dependent pro-apoptotic activity in non-small cell lung cancer. J. Biol. Chem. 2014, 289:5208-5216.
21. Imai S.-i., Guarente L. Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases. Trends Pharmacol. Sci. 2010, 31:212-220.
22. Imai S.-i., Armstrong C.M., Kaeberlein M., Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 2000, 403:795-800.
23. Jiang H., Khan S., Wang Y., Charron G., He B., Sebastian C., Du J., Kim R., Ge E., Mostoslavsky R., et al. SIRT6 regulates TNF-alpha secretion through hydrolysis of long-chain fatty acyl lysine. Nature 2013, 496:110-113.
24. Kim S.Y., Herbst A., Tworkowski K.A., Salghetti S.E., Tansey W.P. Skp2 regulates Myc protein stability and activity. Mol. Cell 2003, 11:1177-1188.
25. Kim H.S., Vassilopoulos A., Wang R.H., Lahusen T., Xiao Z., Xu X., Li C., Veenstra T.D., Li B., Yu H., et al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell 2011, 20:487-499.
26. Kim W.J., Lee J.W., Quan C., Youn H.J., Kim H.M., Bae S.C. Nicotinamide inhibits growth of carcinogen induced mouse bladder tumor and human bladder tumor xenograft through up-regulation of RUNX3 and p300. J. Urol. 2011, 185:2366-2375.
27. Lee J.-H., Choy M.L., Marks P.A. Mechanisms of resistance to histone deacetylase inhibitors. Adv. Cancer Res. 2012, 116:39-86.
28. Liu P.Y., Xu N., Malyukova A., Scarlett C.J., Sun Y.T., Zhang X.D., Ling D., Su S.P., Nelson C., Chang D.K., et al. The histone deacetylase SIRT2 stabilizes Myc oncoproteins. Cell Death Differ. 2013, 20:503-514.
29. Liu Z., Yang T., Li X., Peng T., Hang H.C., Li X.D. Integrative chemical biology approaches for identification and characterization of "erasers" for fatty-acid-acylated lysine residues within proteins. Angew. Chem. Int. Ed. Engl. 2014, 54:1149-1152.
30. Mahajan S.S., Scian M., Sripathy S., Posakony J., Lao U., Loe T.K., Leko V., Thalhofer A., Schuler A.D., Bedalov A., Simon J.A. Development of pyrazolone and isoxazol-5-one cambinol analogues as sirtuin inhibitors. J. Med. Chem. 2014, 57:3283-3294.
31. Marks P.A., Breslow R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat. Biotechnol. 2007, 25:84-90.
32. McCarthy A.R., Sachweh M.C., Higgins M., Campbell J., Drummond C.J., van Leeuwen I.M., Pirrie L., Ladds M.J., Westwood N.J., Lain S. Tenovin-D3, a novel small-molecule inhibitor of sirtuin SirT2, increases p21 (CDKN1A) expression in a p53-independent manner. Mol. Cancer Ther. 2013, 12:352-360.
33. McGlynn L.M., Zino S., MacDonald A.I., Curle J., Reilly J.E., Mohammed Z.M., McMillan D.C., Mallon E., Payne A.P., Edwards J., Shiels P.G. SIRT2: tumour suppressor or tumour promoter in operable breast cancer?. Eur. J. Cancer 2014, 50:290-301.
34. Meyer N., Penn L.Z. Reflecting on 25 years with MYC. Nat. Rev. Cancer 2008, 8:976-990.
35. Neugebauer R.C., Uchiechowska U., Meier R., Hruby H., Valkov V., Verdin E., Sippl W., Jung M. Structure-activity studies on splitomicin derivatives as sirtuin inhibitors and computational prediction of binding mode. J. Med. Chem. 2008, 51:1203-1213.
36. Paul I., Ahmed S.F., Bhowmik A., Deb S., Ghosh M.K. The ubiquitin ligase CHIP regulates c-Myc stability and transcriptional activity. Oncogene 2013, 32:1284-1295.
37. Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W., Yang K., et al. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol. Cell. Proteomics 2011, 10. M111.012658.
38. Rotili D., Tarantino D., Nebbioso A., Paolini C., Huidobro C., Lara E., Mellini P., Lenoci A., Pezzi R., Botta G., et al. Discovery of salermide-related sirtuin inhibitors: binding mode studies and antiproliferative effects in cancer cells including cancer stem cells. J. Med. Chem. 2012, 55:10937-10947.
39. Seifert T., Malo M., Kokkola T., Engen K., Friden-Saxin M., Wallen E.A., Lahtela-Kakkonen M., Jarho E.M., Luthman K. Chroman-4-one- and chromone-based sirtuin 2 inhibitors with antiproliferative properties in cancer cells. J. Med. Chem. 2014, 57:9870-9888.
40. Serrano L., Martinez-Redondo P., Marazuela-Duque A., Vazquez B.N., Dooley S.J., Voigt P., Beck D.B., Kane-Goldsmith N., Tong Q., Rabanal R.M., et al. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation. Genes Dev. 2013, 27:639-653.
41. Shoemaker R.H. The NCI60 human tumour cell line anticancer drug screen. Nat. Rev. Cancer 2006, 6:813-823.
42. Smith B.C., Denu J.M. Mechanism-based Inhibition of Sir2 deacetylases by thioacetyl-lysine peptide. Biochemistry 2007, 46:14478-14486.
43. Soung Y.H., Pruitt K., Chung J. Epigenetic silencing of ARRDC3 expression in basal-like breast cancer cells. Sci. Rep. 2014, 4:3846.
44. Stünkel W., Campbell R.M. Sirtuin 1 (SIRT1): the misunderstood HDAC. J. Biomol. Screen. 2011, 16:1153-1169.
45. Suzuki T., Asaba T., Imai E., Tsumoto H., Nakagawa H., Miyata N. Identification of a cell-active non-peptide sirtuin inhibitor containing N-thioacetyl lysine. Bioorg. Med. Chem. Lett. 2009, 19:5670-5672.
46. Teng Y.B., Jing H., Aramsangtienchai P., He B., Khan S., Hu J., Lin H., Hao Q. Efficient demyristoylase activity of SIRT2 revealed by kinetic and structural studies. Sci. Rep. 2015, 5:8529.
47. Weiss W.A., Taylor S.S., Shokat K.M. Recognizing and exploiting differences between RNAi and small-molecule inhibitors. Nat. Chem. Biol. 2007, 3:739-744.
48. Welcker M., Orian A., Jin J., Grim J.E., Harper J.W., Eisenman R.N., Clurman B.E. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc. Natl. Acad. Sci. USA 2004, 101:9085-9090.
49. Wolfe A.L., Singh K., Zhong Y., Drewe P., Rajasekhar V.K., Sanghvi V.R., Mavrakis K.J.M., Roderick J.E., Van der Meulen J., Schatz J.H., et al. RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer. Nature 2014, 513:65-70.
50. Wu C.H., van Riggelen J., Yetil A., Fan A.C., Bachireddy P., Felsher D.W. Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc. Natl. Acad. Sci. USA 2007, 104:13028-13033.
51. Yang M.H., Laurent G., Bause A.S., Spang R., German N., Haigis M.C., Haigis K.M. HDAC6 and SIRT2 regulate the acetylation state and oncogenic activity of mutant K-RAS. Mol. Cancer Res. 2013, 11:1072-1077.
52. Yoon Y.K., Ali M.A., Wei A.C., Shirazi A.N., Parang K., Choon T.S. Benzimidazoles as new scaffold of sirtuin inhibitors: green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties. Eur. J. Med. Chem. 2014, 83:448-454.
53. Zaharevitz D.W., Holbeck S.L., Bowerman C., Svetlik P.A. COMPARE: a web accessible tool for investigating mechanisms of cell growth inhibition. J. Mol. Graph Model. 2002, 20:297-303.
54. Zhang Y., Au Q., Zhang M., Barber J.R., Ng S.C., Zhang B. Identification of a small molecule SIRT2 inhibitor with selective tumor cytotoxicity. Biochem. Biophys. Res. Commun. 2009, 386:729-733.
55. Zhao D., Zou S.-W., Liu Y., Zhou X., Mo Y., Wang P., Xu Y.-H., Dong B., Xiong Y., Lei Q.-Y., Guan K.-L. Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer. Cancer Cell 2013, 23:464-476.
56. Zhao D., Mo Y., Li M.T., Zou S.W., Cheng Z.L., Sun Y.P., Xiong Y., Guan K.L., Lei Q.Y. NOTCH-induced aldehyde dehydrogenase 1A1 deacetylation promotes breast cancer stem cells. J. Clin. Invest. 2014, 124:5453-5465.
57. Zhu A.Y., Zhou Y., Khan S., Deitsch K.W., Hao Q., Lin H. Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine. ACS Chem. Biol. 2012, 7:155-159.