Small-molecule inhibitors of acetyltransferase p300 identified by high-throughput screening are potent anticancer agents

Molecular Cancer Therapeutics

Volumn 12, Issue 5, 2013, Pages 610-620

  Yang, Heng ^a,e   Pinello, Christie E ^c   Luo, Jian ^a,i   Li, Dawei ^a,f   Wang, Yunfei ^a,g   Zhao, Lisa Y ^a,b   Jahn, Stephan C ^b   Saldanha, Sanjay Adrian ^c,j   Planck, Jamie ^h   Geary, Kyla R ^h   Ma, Haiching ^h   Law, Brian K ^b   Roush, William R ^d   Hodder, Peter ^c,d   Liao, Daiqing ^a,k  

^a UNIVERSITY OF FLORIDA   (United States)

^b UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^c SCRIPPS RESEARCH INSTITUTE   (United States)

^d Department of Chemistry ^*  (United States)

^e BEIJING UNIVERSITY OF CHINESE MEDICINE   (China)

^f SHANDONG UNIVERSITY   (China)

^g NORTHWEST A F UNIVERSITY   (China)

^h REACTION BIOLOGY CORPORATION   (United States)

ⁱ HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^j BRISTOL MYERS SQUIBB   (United States)

^k UNIVERSITY OF FLORIDA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ACYLTRANSFERASE; ACYLTRANSFERASE INHIBITOR; ACYLTRANSFERASE KAT5; ACYLTRANSFERASE KAT6B; ACYLTRANSFERASE KAT7; ANTINEOPLASTIC AGENT; ETOPOSIDE; HISTONE ACETYLTRANSFERASE GCN5; HISTONE ACETYLTRANSFERASE PCAF; HISTONE DEACETYLASE; HISTONE METHYLTRANSFERASE; JANUS KINASE 2; L 002; NSC 764414; PROTEIN P21; STAT3 PROTEIN; UNCLASSIFIED DRUG; VORINOSTAT;

ANIMAL EXPERIMENT; ARTICLE; BREAST CANCER; CANCER INHIBITION; CATALYSIS; CELL VIABILITY; COLON CANCER; CONTROLLED STUDY; CYTOTOXICITY; ENZYME ACTIVITY; ENZYME INHIBITION; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IC 50; LEUKEMIA; LUNG NON SMALL CELL CANCER; LYMPHOMA; MOUSE; NEUROBLASTOMA; NONHUMAN; PANCREAS CANCER; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROSTATE CANCER; TRIPLE NEGATIVE BREAST CANCER; TUMOR XENOGRAFT; WESTERN BLOTTING;

ACETYLATION; ANIMALS; ANTINEOPLASTIC AGENTS; CATALYTIC DOMAIN; CELL LINE; DRUG SCREENING ASSAYS, ANTITUMOR; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INHIBITORY CONCENTRATION 50; MICE; MOLECULAR DOCKING SIMULATION; P300-CBP TRANSCRIPTION FACTORS; PROTEIN BINDING; PROTEIN INTERACTION DOMAINS AND MOTIFS; SMALL MOLECULE LIBRARIES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84877642396     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-12-0930     Document Type: Article

References (49)

1. Eckner R, Ewen ME, Newsome D, Gerdes M, DeCaprio JA, Lawrence JB, et al. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev 1994;8:869-84.
2. Bedford DC, Kasper LH, Fukuyama T, Brindle PK. Target gene context influences the transcriptional requirement for the KAT3 family of CBP and p300 histone acetyltransferases. Epigenetics 2010;5:9-15.
3. Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 1997;90:595-606.
4. Heemers HV, Debes JD, Tindall DJ. The role of the transcriptional coactivator p300 in prostate cancer progression. Adv Exp Med Biol 2008;617:535-40.
5. Isharwal S, Miller MC, Marlow C, Makarov DV, Partin AW, Veltri RW. p300 (histone acetyltransferase) biomarker predicts prostate cancer biochemical recurrence and correlates with changes in epithelia nuclear size and shape. Prostate 2008;68:1097-104.
6. Yokomizo C, Yamaguchi K, Itoh Y, Nishimura T, Umemura A, Minami M, et al. High expression of p300 in HCC predicts shortened overall survival in association with enhanced epithelial mesenchymal transition of HCC cells. Cancer Lett 2011;310:140-7.
7. Li M, Luo RZ, Chen JW, Cao Y, Lu JB, He JH, et al. High expression of transcriptional coactivator p300 correlates with aggressive features and poor prognosis of hepatocellular carcinoma. J Transl Med 2011;9:5.
8. Fermento ME, Gandini NA, Lang CA, Perez JE, Maturi HV, Curino AC, et al. Intracellular distribution of p300 and its differential recruitment to aggresomes in breast cancer. Exp Mol Pathol 2010;88:256-64.
9. Dekker FJ, Haisma HJ. Histone acetyl transferases as emerging drug targets. Drug Discov Today 2009;14:942-8.
10. Yuan ZL, Guan YJ, Chatterjee D, Chin YE. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science 2005; 307:269-73.
11. Chen LF, Mu Y, Greene WC. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB. EMBO J 2002;21: 6539-48.
12. Nie Y, Erion DM, Yuan Z, Dietrich M, Shulman GI, Horvath TL, et al. STAT3 inhibition of gluconeogenesis is downregulated by SirT1. Nat Cell Biol 2009;11:492-500.
13. Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, et al. The JAK2/STAT3 signaling pathway is required for growth of CD44CD24 stem cell-like breast cancer cells in human tumors. J Clin Invest 2011;121:2723-35.
14. Lee JL, Wang MJ, Chen JY. Acetylation and activation of STAT3 mediated by nuclear translocation of CD44. J Cell Biol 2009;185: 949-57.
15. Korkaya H, Liu S, Wicha MS. Regulation of cancer stem cells by cytokine networks: attacking cancer's inflammatory roots. Clin Cancer Res 2011;17:6125-9.
16. Lin YY, Kiihl S, Suhail Y, Liu SY, Chou YH, Kuang Z, et al. Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK. Nature 2012;482:251-5.
17. Lee IH, Finkel T. Regulation of autophagy by the p300 acetyltransferase. J Biol Chem 2009;284:6322-8.
18. Yang Y, Rao R, Shen J, Tang Y, Fiskus W, Nechtman J, et al. Role of acetylation and extracellular location of heat shock protein 90alpha in tumor cell invasion. Cancer Res 2008;68:4833-42.
19. Santana-Davila R, Perez EA. Treatment options for patients with triplenegative breast cancer. J Hematol Oncol 2010;3:42.
20. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011;121:2750-67.
21. Chan CH, Lee SW, Li CF, Wang J, Yang WL, Wu CY, et al. Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis. Nat Cell Biol 2010;12:457-67.
22. Li Q, Zhao LY, Zheng Z, Yang H, Santiago A, Liao D. Inhibition of p53 by adenovirus type 12 E1B-55K deregulates cell cycle control and sensitizes tumor cells to genotoxic agents. J Virol 2011;85: 7976-88.
23. Corsino P, Horenstein N, Ostrov D, Rowe T, Law M, Barrett A, et al. A novel class of cyclin-dependent kinase inhibitors identified by molecular docking act through a unique mechanism. J Biol Chem 2009;284: 29945-55.
24. Shechter D, Dormann HL, Allis CD, Hake SB. Extraction, purification and analysis of histones. Nat Protoc 2007;2:1445-57.
25. Liu X, Wang L, Zhao K, Thompson PR, Hwang Y, Marmorstein R, et al. The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. Nature 2008;451:846-50.
26. Hodder P, Cassaday J, Peltier R, Berry K, Inglese J, Feuston B, et al. Identification of metabotropic glutamate receptor antagonists using an automated high-throughput screening system. Anal Biochem 2003; 313:246-54.
27. Balasubramanyam K, Swaminathan V, Ranganathan A, Kundu TK. Small molecule modulators of histone acetyltransferase p300. J Biol Chem 2003;278:19134-40.
28. Bowers EM, Yan G, Mukherjee C, Orry A, Wang L, Holbert MA, et al. Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Chem Biol 2010; 17:471-82.
29. Ito A, Lai CH, Zhao X, Saito S, Hamilton MH, Appella E, et al. p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. EMBO J 2001;20: 1331-40.
30. Bode AM, Dong Z. Post-translational modification of p53 in tumorigenesis. Nat Rev Cancer 2004;4:793-805.
31. Corcoran RB, Contino G, Deshpande V, Tzatsos A, Conrad C, Benes CH, et al. STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Res 2011;71:5020-9.
32. Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U, et al. Curcumin, a novel p300/CREB-binding proteinspecific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem 2004;279:51163-71.
33. Balasubramanyam K, Altaf M, Varier RA, Swaminathan V, Ravindran A, Sadhale PP, et al. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J Biol Chem 2004;279: 33716-26.
34. Stimson L, Rowlands MG, Newbatt YM, Smith NF, Raynaud FI, Rogers P, et al. Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity. Mol Cancer Ther 2005;4:1521-32.
35. Cole PA. Chemical probes for histone-modifying enzymes. Nat Chem Biol 2008;4:590-7.
36. Wang L, Gural A, Sun XJ, Zhao X, Perna F, Huang G, et al. The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation. Science 2011;333:765-9.
37. Xu CR, Cole PA, Meyers DJ, Kormish J, Dent S, Zaret KS. Chromatin "prepattern" and histone modifiers in a fate choice for liver and pancreas. Science 2011;332:963-6.
38. Santer FR, Hoschele PP, Oh SJ, Erb HH, Bouchal J, Cavarretta IT, et al. Inhibition of the acetyltransferases p300 and CBP reveals a targetable function for p300 in the survival and invasion pathways of prostate cancer cell lines. Mol Cancer Ther 2011;10:1644-55.
39. Boelsterli UA, Ho HK, Zhou S, Leow KY. Bioactivation and hepatotoxicity of nitroaromatic drugs. Curr Drug Metab 2006;7:715-27.
40. Morimoto T, Sunagawa Y, Kawamura T, Takaya T, Wada H, Nagasawa A, et al. The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats. J Clin Invest 2008;118:868-78.
41. He L, Sabet A, Djedjos S, Miller R, Sun X, Hussain MA, et al. Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell 2009;137:635-46.
42. Mantelingu K, Reddy BA, Swaminathan V, Kishore AH, Siddappa NB, Kumar GV, et al. Specific inhibition of p300-HAT alters global gene expression and represses HIV replication. Chem Biol 2007;14: 645-57.
43. Tanaka Y, Naruse I, Hongo T, Xu M, Nakahata T, Maekawa T, et al. Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREB-binding protein. Mech Dev 2000;95:133-45.
44. Yao TP, Oh SP, Fuchs M, Zhou ND, Ch'ng LE, Newsome D, et al. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 1998;93: 361-72.
45. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009;9:798-809.
46. Hecht A, Vleminckx K, Stemmler MP, van Roy F, Kemler R. The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates. EMBO J 2000;19:1839-50.
47. Morris JPT, Wang SC, Hebrok M. KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer 2010;10:683-95.
48. Takemaru KI, Moon RT. The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. J Cell Biol 2000;149: 249-54.
49. Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell 2012;150:12-27.