The BET bromodomain inhibitor, JQ1, facilitates c-FLIP degradation and enhances TRAIL-induced apoptosis independent of BRD4 and c-Myc inhibition

Oncotarget

Volumn 6, Issue 33, 2015, Pages 34669-34679

  Yao, Weilong ^a,b   Yue, Ping ^b   Khuri, Fadlo R ^b   Sun, Shi Yong ^b  

^a Central South University   (China)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; BRD4; C FLIP; C Myc; JQ1; TRAIL

Indexed keywords

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; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; DEATH RECEPTOR 4; DEATH RECEPTOR 5; FLICE INHIBITORY PROTEIN; MYC PROTEIN; PROTEASOME; PROTEIN BRD4; SMALL INTERFERING RNA; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG; (+)-JQ1 COMPOUND; ANTINEOPLASTIC AGENT; AZEPINE DERIVATIVE; BRD4 PROTEIN, HUMAN; CFLAR PROTEIN, HUMAN; MYC PROTEIN, HUMAN; NUCLEAR PROTEIN; TNFSF10 PROTEIN, HUMAN; TRANSCRIPTION FACTOR; TRIAZOLE DERIVATIVE;

APOPTOSIS; ARTICLE; CANCER CELL LINE; CELL SURVIVAL; CONTROLLED STUDY; DRUG MECHANISM; DRUG POTENTIATION; HUMAN; HUMAN CELL; NON SMALL CELL LUNG CANCER; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN STABILITY; WESTERN BLOTTING; DRUG EFFECTS; GENE SILENCING; GENETIC TRANSFECTION; METABOLISM; NEOPLASM; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; APOPTOSIS; AZEPINES; BLOTTING, WESTERN; CASP8 AND FADD-LIKE APOPTOSIS REGULATING PROTEIN; CELL LINE, TUMOR; GENE KNOCKDOWN TECHNIQUES; HUMANS; NEOPLASMS; NUCLEAR PROTEINS; PROTO-ONCOGENE PROTEINS C-MYC; RNA, SMALL INTERFERING; TNF-RELATED APOPTOSIS-INDUCING LIGAND; TRANSCRIPTION FACTORS; TRANSFECTION; TRIAZOLES;

EID: 84946606473     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.5785     Document Type: Article

References (40)

1. Fu LL, Tian M, Li X, Li JJ, Huang J, Ouyang L, Zhang Y and Liu B. Inhibition of BET bromodomains as a therapeutic strategy for cancer drug discovery. Oncotarget. 2015; 6:5501-5516.
2. Shi J and Vakoc CR. The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol Cell. 2014; 54:728-736.
3. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, Kastritis E, Gilpatrick T, Paranal RM, Qi J, Chesi M, Schinzel AC, McKeown MR, Heffernan TP, Vakoc CR, Bergsagel PL, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011; 146:904-917.
4. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, et al. Selective inhibition of BET bromodomains. Nature. 2010; 468:1067-1073.
5. Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, Bergeron L and Sims III RJ. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011; 108:16669-16674.
6. Lockwood WW, Zejnullahu K, Bradner JE and Varmus H. Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins. Proc Natl Acad Sci U S A. 2012; 109:19408-19413.
7. Baker EK, Taylor S, Gupte A, Sharp PP, Walia M, Walsh NC, Zannettino AC, Chalk AM, Burns CJ and Walkley CR. BET inhibitors induce apoptosis through a MYC independent mechanism and synergise with CDK inhibitors to kill osteosarcoma cells. Scientific reports. 2015; 5:10120.
8. Puissant A, Frumm SM, Alexe G, Bassil CF, Qi J, Chanthery YH, Nekritz EA, Zeid R, Gustafson WC, Greninger P, Garnett MJ, McDermott U, Benes CH, Kung AL, Weiss WA, Bradner JE, et al. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013; 3:308-323.
9. Picaud S, Da Costa D, Thanasopoulou A, Filippakopoulos P, Fish PV, Philpott M, Fedorov O, Brennan P, Bunnage ME, Owen DR, Bradner JE, Taniere P, O'Sullivan B, Muller S, Schwaller J, Stankovic T, et al. PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains. Cancer Res. 2013; 73:3336-3346.
10. Patel AJ, Liao CP, Chen Z, Liu C, Wang Y and Le LQ. BET bromodomain inhibition triggers apoptosis of NF1-associated malignant peripheral nerve sheath tumors through Bim induction. Cell Rep. 2014; 6:81-92.
11. Stewart HJ, Horne GA, Bastow S and Chevassut TJ. BRD4 associates with p53 in DNMT3A-mutated leukemia cells and is implicated in apoptosis by the bromodomain inhibitor JQ1. Cancer medicine. 2013; 2:826-835.
12. Gallagher SJ, Mijatov B, Gunatilake D, Tiffen JC, Gowrishankar K, Jin L, Pupo GM, Cullinane C, Prinjha RK, Smithers N, McArthur GA, Rizos H and Hersey P. The epigenetic regulator I-BET151 induces BIM-dependent apoptosis and cell cycle arrest of human melanoma cells. J Invest Dermatol. 2014; 134:2795-2805.
13. Boi M, Gaudio E, Bonetti P, Kwee I, Bernasconi E, Tarantelli C, Rinaldi A, Testoni M, Cascione L, Ponzoni M, Mensah AA, Stathis A, Stussi G, Riveiro ME, Herait P, Inghirami G, et al. The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs. Clin Cancer Res. 2015; 21:1628-1638.
14. Shimamura T, Chen Z, Soucheray M, Carretero J, Kikuchi E, Tchaicha JH, Gao Y, Cheng KA, Cohoon TJ, Qi J, Akbay E, Kimmelman AC, Kung AL, Bradner JE and Wong KK. Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer. Clin Cancer Res. 2013; 19:6183-6192.
15. Bhadury J, Nilsson LM, Muralidharan SV, Green LC, Li Z, Gesner EM, Hansen HC, Keller UB, McLure KG and Nilsson JA. BET and HDAC inhibitors induce similar genes and biological effects and synergize to kill in Myc-induced murine lymphoma. Proc Natl Acad Sci U S A. 2014; 111:E2721-2730.
16. Fiskus W, Sharma S, Qi J, Valenta JA, Schaub LJ, Shah B, Peth K, Portier BP, Rodriguez M, Devaraj SG, Zhan M, Sheng J, Iyer SP, Bradner JE and Bhalla KN. Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014; 13:1142-1154.
17. Lee DH, Qi J, Bradner JE, Said JW, Doan NB, Forscher C, Yang H and Koeffler HP. Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015; 136:2055-2064.
18. Wong C, Laddha SV, Tang L, Vosburgh E, Levine AJ, Normant E, Sandy P, Harris CR, Chan CS and Xu EY. The bromodomain and extra-terminal inhibitor CPI203 enhances the antiproliferative effects of rapamycin on human neuroendocrine tumors. Cell Death Dis. 2014; 5:e1450.
19. Tinsley S, Meja K, Shepherd C and Khwaja A. Synergistic induction of cell death in haematological malignancies by combined phosphoinositide-3-kinase and BET bromodomain inhibition. Br J Haematol. 2015; 170:275-8.
20. Abdulghani J and El-Deiry WS. TRAIL receptor signaling and therapeutics. Expert opinion on therapeutic targets. 2010; 14:1091-1108.
21. Bellail AC, Qi L, Mulligan P, Chhabra V and Hao C. TRAIL agonists on clinical trials for cancer therapy: the promises and the challenges. Rev Recent Clin Trials. 2009; 4:34-41.
22. Lim B, Allen JE, Prabhu VV, Talekar MK, Finnberg NK and El-Deiry WS. Targeting TRAIL in the treatment of cancer: new developments. Expert opinion on therapeutic targets. 2015:1-15.
23. Lemke J, von Karstedt S, Zinngrebe J and Walczak H. Getting TRAIL back on track for cancer therapy. Cell Death Differ. 2014; 21:1350-1364.
24. Wajant H. Targeting the FLICE Inhibitory Protein (FLIP) in cancer therapy. Mol Interv. 2003; 3:124-127.
25. Bagnoli M, Canevari S and Mezzanzanica D. Cellular FLICE-inhibitory protein (c-FLIP) signalling: a key regulator of receptor-mediated apoptosis in physiologic context and in cancer. Int J Biochem Cell Biol. 2010; 42:210-213.
26. Shirley S and Micheau O. Targeting c-FLIP in cancer. Cancer Lett. 2013; 332:141-50.
27. Kim Y, Suh N, Sporn M and Reed JC. An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis. J Biol Chem. 2002; 277:22320-22329.
28. Poukkula M, Kaunisto A, Hietakangas V, Denessiouk K, Katajamaki T, Johnson MS, Sistonen L and Eriksson JE. Rapid turnover of c-FLIPshort is determined by its unique C-terminal tail. J Biol Chem. 2005; 280:27345-27355.
29. Ricci MS, Jin Z, Dews M, Yu D, Thomas-Tikhonenko A, Dicker DT and El-Deiry WS. Direct repression of FLIP expression by c-myc is a major determinant of TRAIL sensitivity. Mol Cell Biol. 2004; 24:8541-8555.
30. Zhang L and Fang B. Mechanisms of resistance to TRAILinduced apoptosis in cancer. Cancer Gene Ther. 2005; 12:228-237.
31. Shirley S and Micheau O. Targeting c-FLIP in cancer. Cancer Lett. 2013; 332:141-150.
32. Zhang G, Plotnikov AN, Rusinova E, Shen T, Morohashi K, Joshua J, Zeng L, Mujtaba S, Ohlmeyer M and Zhou MM. Structure-guided design of potent diazobenzene inhibitors for the BET bromodomains. J Med Chem. 2013; 56:9251-9264.
33. Noel JKIK, Ooike S, Sugahara K, Nakamura H, Daibata M. Development of the BET bromodomain inhibitor OTX015. Mol Cancer Ther. 2014; 12:C244.
34. Ren H, Chen M, Yue P, Tao H, Owonikoko TK, Ramalingam SS, Khuri FR and Sun SY. The combination of RAD001 and NVP-BKM120 synergistically inhibits the growth of lung cancer in vitro and in vivo. Cancer Lett. 2012; 325:139-146.
35. Liu X, Yue P, Schonthal AH, Khuri FR and Sun SY. Cellular FLICE-inhibitory protein down-regulation contributes to celecoxib-induced apoptosis in human lung cancer cells. Cancer Res. 2006; 66:11115-11119.
36. Raja SM, Chen S, Yue P, Acker TM, Lefkove B, Arbiser JL, Khuri FR and Sun SY. The natural product honokiol preferentially inhibits cellular FLICE-inhibitory protein and augments death receptor-induced apoptosis. Mol Cancer Ther. 2008; 7:2212-2223.
37. Zou W, Chen S, Liu X, Yue P, Sporn MB, Khuri FR and Sun SY. c-FLIP downregulation contributes to apoptosis induction by the novel synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me) in human lung cancer cells. Cancer Biol Ther. 2007; 6:1614-1620.
38. Zou W, Liu X, Yue P, Khuri FR and Sun SY. PPARgamma Ligands Enhance TRAIL-induced Apoptosis through DR5 Upregulation and c-FLIP Downregulation in Human Lung Cancer Cells. Cancer Biol Ther. 2007; 6:99-106.
39. Sun SY, Yue P, Dawson MI, Shroot B, Michel S, Lamph WW, Heyman RA, Teng M, Chandraratna RA, Shudo K, Hong WK and Lotan R. Differential effects of synthetic nuclear retinoid receptor-selective retinoids on the growth of human non-small cell lung carcinoma cells. Cancer Res. 1997; 57:4931-4939.
40. Liu X, Yue P, Zhou Z, Khuri FR and Sun SY. Death receptor regulation and celecoxib-induced apoptosis in human lung cancer cells. J Natl Cancer Inst. 2004; 96:1769-1780.