TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo

Oncotarget

Volumn 6, Issue 34, 2015, Pages 36456-36471

  Karpel Massler, Georg ^a   Bâ, Maïmouna ^a   Shu, Chang ^a   Halatsch, Marc Eric ^b   Westhoff, Mike Andrew ^b   Bruce, Jeffrey N ^a   Canoll, Peter ^a   Siegelin, Markus D ^a  

^a NewYork Presbyterian Hospital   (United States)

^b UNIVERSITY HOSPITAL ULM   (Germany)

Author keywords

ABT263; Apoptotic resistance; Glioblastoma; Multi targeting; TIC10 ONC201

Indexed keywords

ANTINEOPLASTIC AGENT; CHAPERONE; DEUBIQUITINASE; NAVITOCLAX; PROTEIN BAG3; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MCL 1; PROTEIN NOXA; PROTEIN USP9X; TRAIL INDUCING COMPOUND 10; UNCLASSIFIED DRUG; ANILINE DERIVATIVE; BCL2L1 PROTEIN, HUMAN; FUSED HETEROCYCLIC RINGS; MCL1 PROTEIN, HUMAN; PROTEIN BCL X; SULFONAMIDE; TIC10 COMPOUND;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER STEM CELL; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENTIATION; DRUG SAFETY; FLOW CYTOMETRY; GLIOBLASTOMA; GLIOBLASTOMA CELL LINE; HISTOPATHOLOGY; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN PROCESSING; PROTEIN SYNTHESIS INHIBITION; TREATMENT DURATION; TUMOR REGRESSION; ANIMAL; ANTAGONISTS AND INHIBITORS; BRAIN NEOPLASMS; DRUG EFFECTS; DRUG SCREENING; FEMALE; MALE; METABOLISM; PATHOLOGY; RANDOMIZATION; SCID MOUSE; SIGNAL TRANSDUCTION;

ANILINE COMPOUNDS; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; BCL-X PROTEIN; BRAIN NEOPLASMS; DRUG SYNERGISM; FEMALE; GLIOBLASTOMA; HETEROCYCLIC COMPOUNDS, 4 OR MORE RINGS; HUMANS; MALE; MAP KINASE SIGNALING SYSTEM; MICE; MICE, SCID; MYELOID CELL LEUKEMIA SEQUENCE 1 PROTEIN; PROTO-ONCOGENE PROTEINS C-BCL-2; RANDOM ALLOCATION; SULFONAMIDES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84946866494     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.5505     Document Type: Article

References (54)

1. Karsy M, Huang T, Kleinman G, Karpel-Massler G. Molecular, histopathological, and genomic variants of glioblastoma. Front Biosci (Landmark Ed). 2014; 19:1065-1087.
2. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352:987-996.
3. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014; 344:1396-1401.
4. Allen JE, Krigsfeld G, Mayes PA, Patel L, Dicker DT, Patel AS, et al. Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects. Sci Transl Med. 2013; 5:171ra117.
5. Allen JE, Krigsfeld G, Patel L, Mayes PA, Dicker DT, Wu GS, et al. Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway. Mol Cancer. 2015; 14:99.
6. Allen JE, Prabhu VV, Talekar M, van den Heuvel AP, Lim B, Dicker DT, et al. Genetic and pharmacological screens converge in identifying FLIP, BCL2, and IAP proteins as key regulators of sensitivity to the TRAIL-inducing anticancer agent ONC201/TIC10. Cancer Res. 2015; 75:1668-1674.
7. Prabhu VV, Allen JE, Dicker DT, El-Deiry WS. Smallmolecule ONC201/TIC10 targets chemotherapy-resistant colorectal cancer stem-like cells in an Akt/Foxo3a/TRAILdependent manner. Cancer Res. 2015; 75:1423-1432.
8. Greer YE, Lipkowitz S. TIC10/ONC201: a bend in the road to clinical development. Oncoscience. 2015; 2:75-76.
9. Davids MS, Letai A. Targeting the B-cell lymphoma/leukemia 2 family in cancer. J Clin Oncol. 2012; 30:3127-3135.
10. Yip KW, Reed JC. Bcl-2 family proteins and cancer. Oncogene. 2008; 27:6398-6406.
11. Gandhi L, Camidge DR, Ribeiro de Oliveira M, Bonomi P, Gandara D, Khaira D, et al. Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol. 2011; 29:909-916.
12. Kipps TJ, Eradat H, Grosicki S, Catalano J, Cosolo W, Dyagil I, et al. A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia. Leuk Lymphoma. 2015; 1-30.
13. Roberts AW, Seymour JF, Brown JR, Wierda WG, Kipps TJ, Khaw SL, et al. Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol. 2011; 30:488-496.
14. Wilson WH, O'Connor OA, Czuczman MS, LaCasce AS, Gerecitano JF, Leonard JP, et al. Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol. 2010; 11:1149-1159.
15. Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, et al. Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med. 1999; 5:157-163.
16. Fulda S, Wick W, Weller M, Debatin KM. Smac agonists sensitize for Apo2L/TRAIL-or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat Med. 2002; 8:808-815.
17. Roth W, Isenmann S, Naumann U, Kugler S, Bahr M, Dichgans J, et al. Locoregional Apo2L/TRAIL eradicates intracranial human malignant glioma xenografts in athymic mice in the absence of neurotoxicity. Biochem Biophys Res Commun. 1999; 265:479-483.
18. Siegelin MD, Dohi T, Raskett CM, Orlowski GM, Powers CM, Gilbert CA, et al. Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells. J Clin Invest. 2011; 121:1349-1360.
19. Kast RE, Karpel-Massler G, Halatsch ME. CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide. Oncotarget. 2014; 5:8052-8082.
20. Jacob NT, Lockner JW, Kravchenko VV, Janda KD. Pharmacophore reassignment for induction of the immunosurveillance cytokine TRAIL. Angew Chem Int Ed Engl. 2014; 53:6628-6631.
21. Tagscherer KE, Fassl A, Campos B, Farhadi M, Kraemer A, Bock BC, et al. Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins. Oncogene. 2008; 27:6646-6656.
22. Cruickshanks N, Hamed HA, Bareford MD, Poklepovic A, Fisher PB, Grant S, et al. Lapatinib and obatoclax kill tumor cells through blockade of ERBB1/3/4 and through inhibition of BCL-XL and MCL-1. Mol Pharmacol. 2012; 81:748-758.
23. Schwickart M, Huang X, Lill JR, Liu J, Ferrando R, French DM, et al. Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature. 2010; 463:103-107.
24. Boiani M, Daniel C, Liu X, Hogarty MD, Marnett LJ. The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737. J Biol Chem. 2013; 288:6980-6990.
25. Domina AM, Vrana JA, Gregory MA, Hann SR, Craig RW. MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol. Oncogene. 2004; 23:5301-5315.
26. Goodwin CM, Rossanese OW, Olejniczak ET, Fesik SW. Myeloid cell leukemia-1 is an important apoptotic survival factor in triple-negative breast cancer. Cell Death Differ. 2015; advance online publication 5 June 2015.
27. Jane EP, Premkumar DR, DiDomenico JD, Hu B, Cheng SY, Pollack IF. YM-155 potentiates the effect of ABT-737 in malignant human glioma cells via survivin and Mcl-1 downregulation in an EGFR-dependent context. Mol Cancer Ther. 2013; 12:326-338.
28. Karpel-Massler G, Shu C, Chau L, Banu M, Halatsch ME, Westhoff MA, et al. Combined inhibition of Bcl-2/Bcl-xL and Usp9X/Bag3 overcomes apoptotic resistance in glioblastoma in vitro and in vivo. Oncotarget. 2015; 6:14507-14521.
29. Konopleva M, Contractor R, Tsao T, Samudio I, Ruvolo PP, Kitada S, et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell. 2006; 10:375-388.
30. Pan R, Ruvolo VR, Wei J, Konopleva M, Reed JC, Pellecchia M, et al. Inhibition of Mcl-1 with the pan-Bcl-2 family inhibitor (-)BI97D6 overcomes ABT-737 resistance in acute myeloid leukemia. Blood. 2015; 126:363-372.
31. Pareja F, Macleod D, Shu C, Crary JF, Canoll PD, Ross AH, et al. PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD. Mol Cancer Res. 2014; 12:987-1001.
32. Premkumar DR, Jane EP, Agostino NR, DiDomenico JD, Pollack IF. Bortezomib-induced sensitization of malignant human glioma cells to vorinostat-induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl-1 cleavage, and DNA damage. Mol Carcinog. 2013; 52:118-133.
33. Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005; 435:677-681.
34. Shoemaker AR, Oleksijew A, Bauch J, Belli BA, Borre T, Bruncko M, et al. A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo. Cancer Res. 2006; 66:8731-8739.
35. Faber AC, Coffee EM, Costa C, Dastur A, Ebi H, Hata AN, et al. mTOR inhibition specifically sensitizes colorectal cancers with KRAS or BRAF mutations to BCL-2/BCL-XL inhibition by suppressing MCL-1. Cancer Discov. 2014; 4:42-52.
36. Festa M, Del Valle L, Khalili K, Franco R, Scognamiglio G, Graziano V, et al. BAG3 protein is overexpressed in human glioblastoma and is a potential target for therapy. Am J Pathol. 2011; 178:2504-2512.
37. Trivigno D, Essmann F, Huber SM, Rudner J. Deubiquitinase USP9x confers radioresistance through stabilization of Mcl-1. Neoplasia. 2012; 14:893-904.
38. Yan J, Zhong N, Liu G, Chen K, Liu X, Su L, et al. Usp9xand Noxa-mediated Mcl-1 downregulation contributes to pemetrexed-induced apoptosis in human non-small-cell lung cancer cells. Cell Death Dis. 2014; 5:e1316.
39. Zhang C, Cai TY, Zhu H, Yang LQ, Jiang H, Dong XW, et al. Synergistic antitumor activity of gemcitabine and ABT-737 in vitro and in vivo through disrupting the interaction of USP9X and Mcl-1. Mol Cancer Ther. 2011; 10:1264-1275.
40. Wang S, Kollipara RK, Srivastava N, Li R, Ravindranathan P, Hernandez E, et al. Ablation of the oncogenic transcription factor ERG by deubiquitinase inhibition in prostate cancer. Proc Natl Acad Sci U S A. 2014; 111:4251-4256.
41. Corcoran RB, Cheng KA, Hata AN, Faber AC, Ebi H, Coffee EM, et al. Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell. 2013; 23:121-128.
42. Lee EF, Czabotar PE, van Delft MF, Michalak EM, Boyle MJ, Willis SN, et al. A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation. J Cell Biol. 2008; 180:341-355.
43. Xiao Y, Nimmer P, Sheppard GS, Bruncko M, Hessler P, Lu X, et al. MCL-1 is a key determinant of breast cancer cell survival: validation of MCL-1 dependency utilizing a highly selective small molecule inhibitor. Mol Cancer Ther. 2015; 14:1837-47.
44. Hauck P, Chao BH, Litz J, Krystal GW. Alterations in the Noxa/Mcl-1 axis determine sensitivity of small cell lung cancer to the BH3 mimetic ABT-737. Mol Cancer Ther. 2009; 8:883-892.
45. Mazumder S, Choudhary GS, Al-Harbi S, Almasan A. Mcl-1 phosphorylation defines ABT-737 resistance that can be overcome by increased NOXA expression in leukemic B cells. Cancer Res. 2012; 72:3069-3079.
46. Mukherjee N, Reuland SN, Lu Y, Luo Y, Lambert K, Fujita M, et al. Combining a BCL2 inhibitor with the retinoid derivative fenretinide targets melanoma cells including melanoma initiating cells. J Invest Dermatol. 2015; 135:842-850.
47. Rooswinkel RW, van de Kooij B, Verheij M, Borst J. Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes resistance mediated by Mcl-1, Bfl-1, or Bcl-B. Cell Death Dis. 2012; 3:e366.
48. Capper D, Gaiser T, Hartmann C, Habel A, Mueller W, Herold-Mende C, et al. Stem-cell-like glioma cells are resistant to TRAIL/Apo2L and exhibit down-regulation of caspase-8 by promoter methylation. Acta Neuropathol. 2009; 117:445-456.
49. Cristofanon S, Fulda S. ABT-737 promotes tBid mitochondrial accumulation to enhance TRAIL-induced apoptosis in glioblastoma cells. Cell Death Dis. 2012; 3:e432.
50. Ishii N, Maier D, Merlo A, Tada M, Sawamura Y, Diserens AC, et al. Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol. 1999; 9:469-479.
51. Karpel-Massler G, Westhoff MA, Zhou S, Nonnenmacher L, Dwucet A, Kast RE, et al. Combined inhibition of HER1/EGFR and RAC1 results in a synergistic antiproliferative effect on established and primary cultured human glioblastoma cells. Mol Cancer Ther. 2013; 12:1783-1795.
52. Karpel-Massler G, Kast RE, Westhoff MA, Dwucet A, Welscher N, Nonnenmacher L, et al. Olanzapine inhibits proliferation, migration and anchorage-independent growth in human glioblastoma cell lines and enhances temozolomide's antiproliferative effect. J Neurooncol. 2015; 122:21-33.
53. Karpel-Massler G, Westhoff MA, Kast RE, Dwucet A, Nonnenmacher L, Wirtz CR, et al. Artesunate enhances the antiproliferative effect of temozolomide on U87MG and A172 glioblastoma cell lines. Anticancer Agents Med Chem. 2014; 14:313-318.
54. Karpel-Massler G, Pareja F, Aime P, Shu C, Chau L, Westhoff MA, et al. PARP inhibition restores extrinsic apoptotic sensitivity in glioblastoma. PLoS One. 2014; 9:e114583.