The intrinsic apoptosis pathways as a target in anticancer therapy

Current Pharmaceutical Biotechnology

Volumn 13, Issue 8, 2012, Pages 1426-1438

  Jendrossek, Verena ^a  

^a UNIVERSITY OF ESSEN MEDICAL SCHOOL   (Germany)

Author keywords

Apoptosis; BCL 2 proteins; BH3 mimetic; Cancer; Extrinsic pathway; Intrinsic pathway

Indexed keywords

4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; APOPTOSIS INDUCING FACTOR; APOPTOSOME; APOPTOTIC PROTEASE ACTIVATING FACTOR 1; BIM PROTEIN; CASPASE; CASPASE 2; CASPASE 8; CASPASE 9; CELECOXIB; CYTOCHROME C; DEATH RECEPTOR; FAS ASSOCIATED DEATH DOMAIN PROTEIN; FAS LIGAND; NAVITOCLAX; OBATOCLAX; OBLIMERSEN; PROTEIN BAD; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN BID; PROTEIN MCL 1; PROTEIN NOXA; PUMA PROTEIN; RAPAMYCIN; SECOND MITOCHONDRIAL ACTIVATOR OF CASPASE; SURVIVIN; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND RECEPTOR;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER RESISTANCE; CARCINOGENESIS; CELL DEATH; CELL HYPOXIA; CELL STRESS; CYTOTOXICITY; DNA DAMAGE; DRUG TOLERABILITY; GENE ACTIVATION; GENOTOXICITY; HUMAN; IONIZING RADIATION; LEUKEMIA; LUNG SMALL CELL CANCER; LYMPHOMA; MOLECULARLY TARGETED THERAPY; MYELODYSPLASTIC SYNDROME; NONHUMAN; ONCOGENE; PROTEIN TARGETING; SIGNAL TRANSDUCTION; SOLID TUMOR; THROMBOCYTOPENIA; TREATMENT FAILURE; TREATMENT RESPONSE; TUMOR MICROENVIRONMENT;

ANTINEOPLASTIC AGENTS; APOPTOSIS; HUMANS; NEOPLASMS; PROTO-ONCOGENE PROTEINS C-BCL-2; SIGNAL TRANSDUCTION;

EID: 84862592304     PISSN: 13892010     EISSN: 18734316     Source Type: Journal    
DOI: 10.2174/138920112800784989     Document Type: Article

References (167)

1. Straus, S.E.; Sneller, M.; Lenardo, M.J.; Puck, J.M.; Strober, W. An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative syndrome. Ann. Intern. Med., 1999, 130 (7), 591-601.
2. Randhawa, S.R.; Chahine, B.G.; Lowery-Nordberg, M.; Cotelingam, J.D.; Casillas, A.M., Underexpression and overexpression of Fas and Fas ligand: a double-edged sword. Ann. Allergy Asthma Immunol., 2010, 104 (4), 286-292.
3. Merino, D.; Bouillet, P. The Bcl-2 family in autoimmune and degenerative disorders. Apoptosis 2009., 14 (4), 570-583.
4. Danial, N.N.; Walensky, L.D.; Zhang, C.Y.; Choi, C.S.; Fisher, J.K.; Molina, A.J.; Datta, S.R.; Pitter, K. L.; Bird, G. H.; Wikstrom, J.D.; Deeney, J.T.; Robertson, K.; Morash, J.; Kulkarni, A.; Neschen, S.; Kim, S.; Greenberg, M.E.; Corkey, B.E.; Shirihai, O.S.; Shulman, G.I.; Lowell, B.B.; Korsmeyer, S.J. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat. Med. 2008., 14 (2), 144-153.
5. Dorn, G.W., 2nd. Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling. Cardiovasc. Res., 2009, 81 (3), 465-473.
6. Scarabelli, T.M.; Knight, R.; Stephanou, A.; Townsend, P.; Chen-Scarabelli, C.; Lawrence, K.; Gottlieb, R.; Latchman, D.; Narula, J. Clinical implications of apoptosis in ischemic myocardium. Curr. Probl. Cardiol., 2006, 31 (3), 181-264.
7. Doonan, F.; Cotter, T.G. Apoptosis: a potential therapeutic target for retinal degenerations. Curr. Neurovasc. Res., 2004, 1 (1), 41-53.
8. Lowe, S.W.; Lin, A.W. Apoptosis in cancer. Carcinogenesis, 2000, 21 (3), 485-495.
9. Lowe, S.W.; Cepero, E.; Evan, G. Intrinsic tumour suppression. Nature, 2004, 432 (7015), 307-15.
10. Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell, 2000, 100 (1), 57-70.
11. Gatenby, R.A.; Gillies, R.J. A microenvironmental model of carcinogenesis. Nat. Rev. Cancer 2008, 8 (1), 56-61.
12. Weinmann, M.; Jendrossek, V.; Guner, D.; Goecke, B.; Belka, C. Cyclic exposure to hypoxia and reoxygenation selects for tumor cells with defects in mitochondrial apoptotic pathways. Faseb J. 2004, 18 (15), 1906-1908 Epub 2004 Sep 28.
13. Igney, F.H.; Krammer, P.H. Death and anti-death: tumour resistance to apoptosis. Nat. Rev. Cancer, 2002, 2 (4), 277-288.
14. Reed, J.C. Apoptosis-targeted therapies for cancer. Cancer Cell, 2003, 3 (1), 17-22.
15. Adams, J.M.; Cory, S., The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene, 2007, 26 (9), 1324-1337.
16. Degterev, A.; Boyce, M.; Yuan, J. A decade of caspases. Oncogene 2003, 22 (53), 8543-8567.
17. Boatright, K.M.; Salvesen, G.S. Mechanisms of caspase activation. Curr. Opin. Cell Biol., 2003, 15 (6), 725-731.
18. Hengartner, M.O. The biochemistry of apoptosis. Nature, 2000, 407 (6805), 770-776.
19. Jin, Z.; El-Deiry, W.S. Overview of cell death signaling pathways. Cancer Biol. Ther., 2005, 4 (2), 139-163.
20. Ashkenazi, A. Directing cancer cells to self-destruct with proapoptotic receptor agonists. Nat. Rev. Drug Discov., 2008, 7 (12), 1001-1012.
21. Li, H.; Zhu, H.; Xu, C.J.; Yuan, J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell, 1998, 94 (4), 491-501.
22. Yin, X. M.; Wang, K.; Gross, A.; Zhao, Y.; Zinkel, S.; Klocke, B.; Roth, K.A.; Korsmeyer, S.J. Bid-deficient mice are resistant to Fasinduced hepatocellular apoptosis. Nature, 1999, 400 (6747), 886-891.
23. Fulda, S.; Galluzzi, L.; Kroemer, G. Targeting mitochondria for cancer therapy. Nat. Rev. Drug Discov., 2010, 9 (6), 447-464.
24. Chipuk, J.E.; Moldoveanu, T.; Llambi, F.; Parsons, M.J.; Green, D.R. The BCL-2 family reunion. Mol. Cell, 2010, 37 (3), 299-310.
25. Garrido, C.; Galluzzi, L.; Brunet, M.; Puig, P.E.; Didelot, C.; Kroemer, G. Mechanisms of cytochrome c release from mitochondria. Cell Death Differ., 2006, 13 (9), 1423-1433.
26. Riedl, S.J.; Salvesen, G.S. The apoptosome: signalling platform of cell death. Nat. Rev. Mol. Cell Biol. 2007, 8 (5), 405-413.
27. Oberst, A.; Bender, C.; Green, D.R. Living with death: the evolution of the mitochondrial pathway of apoptosis in animals. Cell Death Differ., 2008, 15 (7), 1139-1146.
28. Bao, Q.; Shi, Y. Apoptosome: a platform for the activation of initiator caspases. Cell Death Differ., 2007, 14 (1), 56-65.
29. Kroemer, G.; Galluzzi, L.; Brenner, C. Mitochondrial membrane permeabilization in cell death. Physiol. Rev., 2007, 87 (1), 99-163.
30. Belka, C.; Rudner, J.; Wesselborg, S.; Stepczynska, A.; Marini, P.; Lepple-Wienhues, A.; Faltin, H.; Bamberg, M.; Budach, W.; Schulze-Osthoff, K. Differential role of caspase-8 and BID activation during radiation- and CD95-induced apoptosis. Oncogene, 2000, 19 (9), 1181-1190.
31. Shelton, S.N.; Shawgo, M.E.; Robertson, J.D. Cleavage of Bid by executioner caspases mediates feed forward amplification of mitochondrial outer membrane permeabilization during genotoxic stress-induced apoptosis in Jurkat cells. J. Biol. Chem., 2009, 284 (17), 11247-11255.
32. Festjens, N.; Cornelis, S.; Lamkanfi, M.; Vandenabeele, P. Caspase-containing complexes in the regulation of cell death and inflammation. Biol. Chem., 2006, 387 (8), 1005-1016.
33. Tinel, A.; Tschopp, J. The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science 2004, 304 (5672), 843-846.
34. Guo, Y.; Srinivasula, S.M.; Druilhe, A.; Fernandes-Alnemri, T.; Alnemri, E.S. Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. J. Biol. Chem., 2002, 277 (16), 13430-13437.
35. Krumschnabel, G.; Sohm, B.; Bock, F.; Manzl, C.; Villunger, A. The enigma of caspase-2: the laymen's view. Cell Death Differ., 2009, 16 (2), 195-207.
36. Ren, J.; Shi, M.; Liu, R.; Yang, Q.H.; Johnson, T.; Skarnes, W.C.; Du, C. The Birc6 (Bruce) gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development. Proc. Natl. Acad. Sci. USA., 2005, 102 (3), 565-570.
37. Janssens, S.; Tinel, A.; Lippens, S.; Tschopp, J. PIDD mediates NF-kappaB activation in response to DNA damage. Cell 2005, 123 (6), 1079-1092.
38. Salvesen, G.S.; Duckett, C.S. IAP proteins: blocking the road to death's door. Nat. Rev. Mol. Cell Biol., 2002, 3 (6), 401-410.
39. Eckelman, B.P.; Salvesen, G.S.; Scott, F.L. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep., 2006, 7 (10), 988-994.
40. Hunter, A.M.; LaCasse, E.C.; Korneluk, R.G. The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis 2007, 12 (9), 1543-1568.
41. Srinivasula, S.M.; Hegde, R.; Saleh, A.; Datta, P.; Shiozaki, E.; Chai, J.; Lee, R. A.; Robbins, P. D.; Fernandes-Alnemri, T.; Shi, Y.; Alnemri, E. S. A conserved XIAP-interaction motif in caspase- 9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature, 2001, 410 (6824), 112-116.
42. Certo, M.; Del Gaizo Moore, V.; Nishino, M.; Wei, G.; Korsmeyer, S.; Armstrong, S.A.; Letai, A. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 2006, 9 (5), 351-365.
43. Youle, R.J.; Strasser, A. The BCL-2 protein family: opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 2008, 9 (1), 47-59.
44. Yip, K.W.; Reed, J.C. Bcl-2 family proteins and cancer. Oncogene 2008, 27 (50), 6398-6406.
45. Green, D.R.; Evan, G.I. A matter of life and death. Cancer Cell, 2002, 1 (1), 19-30
46. Franke, J.C.; Plotz, M.; Prokop, A.; Geilen, C.C.; Schmalz, H.G.; Eberle, J. New caspase-independent but ROS-dependent apoptosis pathways are targeted in melanoma cells by an iron-containing cytosine analogue. Biochem. Pharmacol. 2010, 79 (4), 575-586.
47. Leo, C.; Horn, L.C.; Rauscher, C.; Hentschel, B.; Richter, C.E.; Schutz, A.; Leo, C.P.; Hockel, M. Lack of apoptotic protease activating factor-1 expression and resistance to hypoxia-induced apoptosis in cervical cancer. Clin. Cancer Res., 2007, 13 (4), 1149-1153.
48. Anichini, A.; Mortarini, R.; Sensi, M.; Zanon, M. APAF-1 signaling in human melanoma. Cancer Lett., 2006, 238 (2), 168-179.
49. Hajra, K.M.; Liu, J.R. Apoptosome dysfunction in human cancer. Apoptosis 2004, 9 (6), 691-704.
50. Karst, A.M.; Li, G. BH3-only proteins in tumorigenesis and malignant melanoma. Cell Mol. Life Sci. 2007, 64 (3), 318-330.
51. Fernandez-Luna, J.L. Regulation of pro-apoptotic BH3-only proteins and its contribution to cancer progression and chemoresistance. Cell Signal 2008, 20 (11), 1921-1926.
52. Ho, L.H.; Taylor, R.; Dorstyn, L.; Cakouros, D.; Bouillet, P.; Kumar, S. A tumor suppressor function for caspase-2. Proc. Natl. Acad. Sci. USA., 2009, 106 (13), 5336-5341.
53. Kumar, S. Caspase 2 in apoptosis, the DNA damage response and tumour suppression: enigma no more? Nat. Rev. Cancer, 2009, 9 (12), 897-903.
54. Pingoud-Meier, C.; Lang, D.; Janss, A.J.; Rorke, L.B.; Phillips, P.C.; Shalaby, T.; Grotzer, M.A. Loss of caspase-8 protein expression correlates with unfavorable survival outcome in childhood medulloblastoma. Clin. Cancer Res., 2003, 9 (17), 6401-6409.
55. Teitz, T.; Lahti, J.M.; Kidd, V.J. Aggressive childhood neuroblastomas do not express caspase-8: an important component of programmed cell death. J. Mol. Med., 2001, 79 (8), 428-436.
56. Vaux, D.L.; Cory, S.; Adams, J.M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature, 1988, 335 (6189), 440-442.
57. Wei, G.; Twomey, D.; Lamb, J.; Schlis, K.; Agarwal, J.; Stam, R.W.; Opferman, J.T.; Sallan, S.E.; den Boer, M.L.; Pieters, R.; Golub, T.R.; Armstrong, S.A., Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance. Cancer Cell, 2006, 10 (4), 331-342.
58. Holleman, A.; den Boer, M.L.; de Menezes, R.X.; Cheok, M.H.; Cheng, C.; Kazemier, K.M.; Janka-Schaub, G.E.; Gobel, U.; Graubner, U.B.; Evans, W.E.; Pieters, R. The expression of 70 apoptosis genes in relation to lineage, genetic subtype, cellular drug resistance, and outcome in childhood acute lymphoblastic leukemia. Blood, 2006, 107 (2), 769-776.
59. Wagner, M.; Schmelz, K.; Wuchter, C.; Ludwig, W.D.; Dorken, B.; Tamm, I. In vivo expression of survivin and its splice variant survivin-2B: impact on clinical outcome in acute myeloid leukemia. Int. J. Cancer, 2006, 119 (6), 1291-1297.
60. Li, F. Role of survivin and its splice variants in tumorigenesis. Br. J. Cancer, 2005, 92 (2), 212-216.
61. Elkholi, R.; Floros, K.V.; Chipuk, J.E. The Role of BH3-Only Proteins in Tumor Cell Development, Signaling, and Treatment. Genes Cancer, 2011, 2 (5), 523-537.
62. Belka, C.; Jendrossek, V.; Pruschy, M.; Vink, S.; Verheij, M.; Budach, W. Apoptosis-modulating agents in combination with radiotherapy-current status and outlook. Int. J. Radiat. Oncol. Biol. Phys. 2004, 58 (2), 542-554.
63. Hoyer-Hansen, M.; Jaattela, M. Autophagy: an emerging target for cancer therapy. Autophagy 2008, 4 (5), 574-580.
64. Hu, X.; Xuan, Y. Bypassing cancer drug resistance by activating multiple death pathways--a proposal from the study of circumventing cancer drug resistance by induction of necroptosis. Cancer Lett., 2008, 259 (2), 127-137.
65. Fulda, S.; Debatin, K.M. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, 2006, 25 (34), 4798-4811.
66. Marini, P.; Budach, W.; Niyazi, M.; Junginger, D.; Stickl, S.; Jendrossek, V.; Belka, C. Combination of the pro-apoptotic TRAIL-receptor antibody mapatumumab with ionizing radiation strongly increases long-term tumor control under ambient and hypoxic conditions. Int. J. Radiat. Oncol. Biol. Phys., 2009, 75 (1), 198-202.
67. van Delft, M.F.; Wei, A.H.; Mason, K.D.; Vandenberg, C.J.; Chen, L.; Czabotar, P.E.; Willis, S.N.; Scott, C.L.; Day, C.L.; Cory, S.; Adams, J.M.; Roberts, A.W.; Huang, D.C. The BH3 mimetic ABT- 737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell., 2006, 10 (5), 389-399.
68. Konopleva, M.; Watt, J.; Contractor, R.; Tsao, T.; Harris, D.; Estrov, Z.; Bornmann, W.; Kantarjian, H.; Viallet, J.; Samudio, I.; Andreeff, M. Mechanisms of antileukemic activity of the novel Bcl-2 homology domain-3 mimetic GX15-070 (obatoclax). Cancer Res., 2008, 68 (9), 3413-3420.
69. Walensky, L.D.; Kung, A.L.; Escher, I.; Malia, T.J.; Barbuto, S.; Wright, R.D.; Wagner, G.; Verdine, G.L.; Korsmeyer, S.J. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 2004, 305 (5689), 1466-1470.
70. Chonghaile, T.N.; Letai, A. Mimicking the BH3 domain to kill cancer cells. Oncogene, 2008, 27 Suppl 1, S149-157.
71. Dai, Y.; Liu, M.; Tang, W.; DeSano, J.; Burstein, E.; Davis, M.; Pienta, K.; Lawrence, T.; Xu, L. Molecularly targeted radiosensitization of human prostate cancer by modulating inhibitor of apoptosis. Clin. Cancer Res., 2008, 14 (23), 7701-7710.
72. Dean, E.; Jodrell, D.; Connolly, K.; Danson, S.; Jolivet, J.; Durkin, J.; Morris, S.; Jowle, D.; Ward, T.; Cummings, J.; Dickinson, G.; Aarons, L.; Lacasse, E.; Robson, L.; Dive, C.; Ranson, M. Phase I trial of AEG35156 administered as a 7-day and 3-day continuous intravenous infusion in patients with advanced refractory cancer. J. Clin. Oncol., 2009, 27 (10), 1660-1666.
73. Giagkousiklidis, S.; Vogler, M.; Westhoff, M.A.; Kasperczyk, H.; Debatin, K.M.; Fulda, S. Sensitization for gamma-irradiationinduced apoptosis by second mitochondria-derived activator of caspase. Cancer Res., 2005, 65 (22), 10502-10513.
74. Ledgerwood, E.C.; Morison, I. M. Targeting the apoptosome for cancer therapy. Clin. Cancer Res., 2009, 15 (2), 420-424.
75. Tuma, R.S. Agents targeting apoptosis show promise in early trials. J. Natl. Cancer Inst., 2009, 101 (3), 138-139.
76. Leong, S.; Cohen, R.B.; Gustafson, D.L.; Langer, C.J.; Camidge, D.R.; Padavic, K.; Gore, L.; Smith, M.; Chow, L.Q.; von Mehren, M.; O'Bryant, C.; Hariharan, S.; Diab, S.; Fox, N.L.; Miceli, R.; Eckhardt, S.G. Mapatumumab, an antibody targeting TRAIL-R1, in combination with paclitaxel and carboplatin in patients with advanced solid malignancies: results of a phase I and pharmacokinetic study. J. Clin. Oncol., 2009, 27 (26), 4413-4421.
77. Hotte, S.J.; Hirte, H.W.; Chen, E.X.; Siu, L.L.; Le, L.H.; Corey, A.; Iacobucci, A.; MacLean, M.; Lo, L.; Fox, N.L.; Oza, A.M. A phase 1 study of mapatumumab (fully human monoclonal antibody to TRAIL-R1) in patients with advanced solid malignancies. Clin. Cancer Res., 2008, 14 (11), 3450-3455.
78. Trarbach, T.; Moehler, M.; Heinemann, V.; Kohne, C.H.; Przyborek, M.; Schulz, C.; Sneller, V.; Gallant, G.; Kanzler, S. Phase II trial of mapatumumab, a fully human agonistic monoclonal antibody that targets and activates the tumour necrosis factor apoptosis-inducing ligand receptor-1 (TRAIL-R1), in patients with refractory colorectal cancer. Br. J. Cancer, 2010, 102 (3), 506-512.
79. Schimmer, A.D.; Estey, E.H.; Borthakur, G.; Carter, B.Z.; Schiller, G.J.; Tallman, M.S.; Altman, J. K.; Karp, J.E.; Kassis, J.; Hedley, D.W.; Brandwein, J.; Xu, W.; Mak, D.H.; LaCasse, E.; Jacob, C.; Morris, S.J.; Jolivet, J.; Andreeff, M. Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia. J. Clin. Oncol., 2009, 27 (28), 4741-4746.
80. Giaccone, G.; Zatloukal, P.; Roubec, J.; Floor, K.; Musil, J.; Kuta, M.; van Klaveren, R.J.; Chaudhary, S.; Gunther, A.; Shamsili, S. Multicenter phase II trial of YM155, a small-molecule suppressor of survivin, in patients with advanced, refractory, non-small-cell lung cancer. J. Clin. Oncol., 2009, 27 (27), 4481-4486.
81. Raab, R.; Sparano, J.A.; Ocean, A.J.; Christos, P.; Ramirez, M.; Vinciguerra, V.; Kaubisch, A. A phase I trial of oblimersen sodium in combination with cisplatin and 5-fluorouracil in patients with advanced esophageal, gastroesophageal junction, and gastric carcinoma. Am. J. Clin. Oncol., 2010, 33 (1), 61-65.
82. O'Brien, S.; Moore, J.O.; Boyd, T.E.; Larratt, L.M.; Skotnicki, A.B.; Koziner, B.; Chanan-Khan, A. A.; Seymour, J.F.; Gribben, J.; Itri, L.M.; Rai, K.R. 5-year survival in patients with relapsed or refractory chronic lymphocytic leukemia in a randomized, phase III trial of fludarabine plus cyclophosphamide with or without oblimersen. J. Clin. Oncol., 2009, 27 (31), 5208-5212.
83. O'Brien, S.M.; Claxton, D.F.; Crump, M.; Faderl, S.; Kipps, T.; Keating, M.J.; Viallet, J.; Cheson, B.D. Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia. Blood, 2009, 113 (2), 299-305.
84. Lindsten, T.; Ross, A.J.; King, A.; Zong, W.X.; Rathmell, J.C.; Shiels, H.A.; Ulrich, E.; Waymire, K. G.; Mahar, P.; Frauwirth, K.; Chen, Y.; Wei, M.; Eng, V.M.; Adelman, D.M.; Simon, M.C.; Ma, A.; Golden, J.A.; Evan, G.; Korsmeyer, S.J.; MacGregor, G.R.; Thompson, C.B. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol. Cell, 2000, 6 (6), 1389-1399.
85. Huang, D.C.; Strasser, A. BH3-Only proteins-essential initiators of apoptotic cell death. Cell, 2000, 103 (6), 839-842.
86. Sattler, M.; Liang, H.; Nettesheim, D.; Meadows, R.P.; Harlan, J.E.; Eberstadt, M.; Yoon, H.S.; Shuker, S.B.; Chang, B.S.; Minn, A.J.; Thompson, C.B.; Fesik, S.W. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 1997, 275 (5302), 983-986.
87. Vander Heiden, M.G.; Chandel, N.S.; Williamson, E.K.; Schumacker, P.T.; Thompson, C.B. Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell, 1997, 91 (5), 627-637.
88. Willis, S.N.; Chen, L.; Dewson, G.; Wei, A.; Naik, E.; Fletcher, J.I.; Adams, J.M.; Huang, D.C. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev., 2005, 19 (11), 1294-1305.
89. Rudner, J.; Elsaesser, S.J.; Jendrossek, V.; Huber, S.M. Antiapoptotic Bcl-2 fails to form efficient complexes with pro-apoptotic Bak to protect from Celecoxib-induced apoptosis. Biochem. Pharmacol., 2011, 81 (1), 32-42.
90. Willis, S.N.; Fletcher, J.I.; Kaufmann, T.; van Delft, M.F.; Chen, L.; Czabotar, P.E.; Ierino, H.; Lee, E.F.; Fairlie, W.D.; Bouillet, P.; Strasser, A.; Kluck, R.M.; Adams, J.M.; Huang, D.C. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science, 2007, 315 (5813), 856-859.
91. Edlich, F.; Banerjee, S.; Suzuki, M.; Cleland, M.M.; Arnoult, D.; Wang, C.; Neutzner, A.; Tjandra, N.; Youle, R.J. Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol. Cell, 2011, 145 (1), 104-116.
92. Bouillet, P.; Strasser, A. BH3-only proteins - evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death. J. Cell Sci., 2002, 115 (Pt 8), 1567-1574.
93. Nakano, K.; Vousden, K.H. PUMA, a Novel Proapoptotic Gene, Is Induced by p53. Mol. Cell, 2001, 7 (3), 683-694.
94. Oda, E.; Ohki, R.; Murasawa, H.; Nemoto, J.; Shibue, T.; Yamashita, T.; Tokino, T.; Taniguchi, T.; Tanaka, N. Noxa, a BH3- only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science, 2000, 288 (5468), 1053-1058.
95. Puthalakath, H.; O'Reilly, L.A.; Gunn, P.; Lee, L.; Kelly, P.N.; Huntington, N.D.; Hughes, P.D.; Michalak, E.M.; McKimm-Breschkin, J.; Motoyama, N.; Gotoh, T.; Akira, S.; Bouillet, P.; Strasser, A. ER stress triggers apoptosis by activating BH3-only protein Bim. Cell, 2007, 129 (7), 1337-1349.
96. Altman, B.J.; Wofford, J.A.; Zhao, Y.; Coloff, J.L.; Ferguson, E.C.; Wieman, H.L.; Day, A.E.; Ilkayeva, O.; Rathmell, J.C. Autophagy provides nutrients but can lead to Chop-dependent induction of Bim to sensitize growth factor-deprived cells to apoptosis. Mol. Biol. Cell, 2009, 20 (4), 1180-1191.
97. Ekoff, M.; Kaufmann, T.; Engstrom, M.; Motoyama, N.; Villunger, A.; Jonsson, J.I.; Strasser, A.; Nilsson, G. The BH3-only protein Puma plays an essential role in cytokine deprivation induced apoptosis of mast cells. Blood, 2007, 110 (9), 3209-3217.
98. Chen, L.; Willis, S.N.; Wei, A.; Smith, B.J.; Fletcher, J.I.; Hinds, M.G.; Colman, P.M.; Day, C.L.; Adams, J.M.; Huang, D.C. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol. Cell, 2005, 17 (3), 393-403.
99. Kuwana, T.; Bouchier-Hayes, L.; Chipuk, J.E.; Bonzon, C.; Sullivan, B.A.; Green, D.R.; Newmeyer, D.D. BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol. Cell, 2005, 17 (4), 525-535.
100. Bouillet, P.; Huang, D.C.; O'Reilly, L.A.; Puthalakath, H.; O'Connor, L.; Cory, S.; Adams, J.M.; Strasser, A. The role of the pro-apoptotic Bcl-2 family member bim in physiological cell death. Ann. N. Y. Acad. Sci, 2000, 926, 83-89.
101. Galonek, H.L.; Hardwick, J.M. Upgrading the BCL-2 network. Nat. Cell. Biol., 2006, 8 (12), 1317-1319.
102. Letai, A.; Bassik, M.C.; Walensky, L.D.; Sorcinelli, M.D.; Weiler, S.; Korsmeyer, S.J. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell, 2002, 2 (3), 183-192.
103. Wei, M.C.; Lindsten, T.; Mootha, V.K.; Weiler, S.; Gross, A.; Ashiya, M.; Thompson, C.B.; Korsmeyer, S.J. TBID, a membranetargeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev.; 2000, 14 (16), 2060-2071.
104. Jabbour, A.M.; Heraud, J.E.; Daunt, C.P.; Kaufmann, T.; Sandow, J.; O'Reilly, L.A.; Callus, B.A.; Lopez, A.; Strasser, A.; Vaux, D.L.; Ekert, P.G. Puma indirectly activates Bax to cause apoptosis in the absence of Bid or Bim. Cell Death Differ., 2009, 16 (4), 555-563.
105. Kim, H.; Tu, H.C.; Ren, D.; Takeuchi, O.; Jeffers, J.R.; Zambetti, G.P.; Hsieh, J.J.; Cheng, E.H. Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol. Cell, 2009, 36 (3), 487-499.
106. Ruffolo, S.C.; Shore, G.C. BCL-2 selectively interacts with the BID-induced open conformer of BAK, inhibiting BAK autooligomerization. J. Biol. Chem., 2003, 278 (27), 25039-25045.
107. Kim, H.; Rafiuddin-Shah, M.; Tu, H.C.; Jeffers, J.R.; Zambetti, G.P.; Hsieh, J.J.; Cheng, E.H. Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies. Nat. Cell Biol. 2006, 8 (12), 1348-1358.
108. Merino, D.; Giam, M.; Hughes, P.D.; Siggs, O.M.; Heger, K.; O'Reilly, L.A.; Adams, J.M.; Strasser, A.; Lee, E.F.; Fairlie, W.D.; Bouillet, P. The role of BH3-only protein Bim extends beyond inhibiting Bcl-2-like prosurvival proteins. J. Cell Biol., 2009, 186 (3), 355-362.
109. Hossini, A.M.; Eberle, J. Apoptosis induction by Bcl-2 proteins independent of the BH3 domain. Biochem, Pharmacol., 2008, 76 (11), 1612-1619.
110. Hossini, A.M.; Geilen, C.C.; Fecker, L.F.; Daniel, P.T.; Eberle, J. A novel Bcl-x splice product, Bcl-xAK, triggers apoptosis in human melanoma cells without BH3 domain. Oncogene, 2006, 25 (15), 2160-2169.
111. Derenne, S.; Monia, B.; Dean, N.M.; Taylor, J.K.; Rapp, M.J.; Harousseau, J.L.; Bataille, R.; Amiot, M. Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells. Blood, 2002, 100 (1), 194-199.
112. Warr, M.R.; Shore, G.C. Unique biology of Mcl-1: therapeutic opportunities in cancer. Curr. Mol. Med., 2008, 8 (2), 138-147.
113. Fesik, S.W. Promoting apoptosis as a strategy for cancer drug discovery. Nat. Rev. Cancer, 2005, 5 (11), 876-885.
114. Debatin, K.M.; Poncet, D.; Kroemer, G. Chemotherapy: targeting the mitochondrial cell death pathway. Oncogene, 2002, 21 (57), 8786-8803.
115. Amundson, S.A.; Myers, T.G.; Scudiero, D.; Kitada, S.; Reed, J.C.; Fornace, A.J. Jr. An informatics approach identifying markers of chemosensitivity in human cancer cell lines. Cancer Res., 2000, 60 (21), 6101-6110.
116. Kang, M.H.; Reynolds, C.P. Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin. Cancer Res., 2009, 15 (4), 1126-1132.
117. Bedikian, A.Y.; Millward, M.; Pehamberger, H.; Conry, R.; Gore, M.; Trefzer, U.; Pavlick, A.C.; DeConti, R.; Hersh, E.M.; Hersey, P.; Kirkwood, J.M.; Haluska, F.G. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J. Clin. Oncol., 2006, 24 (29), 4738-4745.
118. Chanan-Khan, A.A.; Niesvizky, R.; Hohl, R.J.; Zimmerman, T.M.; Christiansen, N.P.; Schiller, G. J.; Callander, N.; Lister, J.; Oken, M.; Jagannath, S. Phase III randomised study of dexamethasone with or without oblimersen sodium for patients with advanced multiple myeloma. Leuk. Lymphoma, 2009, 50 (4), 559-565.
119. Sternberg, C.N.; Dumez, H.; Van Poppel, H.; Skoneczna, I.; Sella, A.; Daugaard, G.; Gil, T.; Graham, J.; Carpentier, P.; Calabro, F.; Collette, L.; Lacombe, D. Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer. Ann. Oncol., 2009, 20 (7), 1264-1269.
120. Walensky, L.D.; Pitter, K.; Morash, J.; Oh, K.J.; Barbuto, S.; Fisher, J.; Smith, E.; Verdine, G.L.; Korsmeyer, S. J. A stapled BID BH3 helix directly binds and activates BAX. Mol. Cell, 2006, 24 (2), 199-210.
121. Stewart, M.L.; Fire, E.; Keating, A.E.; Walensky, L.D. The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. Nat. Chem. Biol., 2010, 6 (8), 595-601.
122. Oltersdorf, T.; Elmore, S.W.; Shoemaker, A.R.; Armstrong, R.C.; Augeri, D.J.; Belli, B.A.; Bruncko, M.; Deckwerth, T.L.; Dinges, J.; Hajduk, P.J.; Joseph, M.K.; Kitada, S.; Korsmeyer, S.J.; Kunzer, A.R.; Letai, A.; Li, C.; Mitten, M.J.; Nettesheim, D.G.; Ng, S.; Nimmer, P.M.; O'Connor, J.M.; Oleksijew, A.; Petros, A.M.; Reed, J.C.; Shen, W.; Tahir, S.K.; Thompson, C.B.; Tomaselli, K.J.; Wang, B.; Wendt, M.D.; Zhang, H.; Fesik, S.W.; Rosenberg, S.H. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature, 2005, 435 (7042), 677-681.
123. Konopleva, M.; Contractor, R.; Tsao, T.; Samudio, I.; Ruvolo, P.P.; Kitada, S.; Deng, X.; Zhai, D.; Shi, Y.X.; Sneed, T.; Verhaegen, M.; Soengas, M.; Ruvolo, V.R.; McQueen, T.; Schober, W.D.; Watt, J.C.; Jiffar, T.; Ling, X.; Marini, F.C.; Harris, D.; Dietrich, M.; Estrov, Z.; McCubrey, J.; May, W.S.; Reed, J.C.; Andreeff, M. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell, 2006, 10 (5), 375-388.
124. Vogler, M.; Dinsdale, D.; Sun, X.M.; Young, K.W.; Butterworth, M.; Nicotera, P.; Dyer, M.J.; Cohen, G.M. A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells. Cell Death Differ., 2008, 15 (5), 820-830.
125. Del Gaizo Moore, V.; Schlis, K.D.; Sallan, S.E.; Armstrong, S.A.; Letai, A. BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia. Blood, 2008, 111 (4), 2300-2309.
126. Kuroda, J.; Kimura, S.; Andreeff, M.; Ashihara, E.; Kamitsuji, Y.; Yokota, A.; Kawata, E.; Takeuchi, M.; Tanaka, R.; Murotani, Y.; Matsumoto, Y.; Tanaka, H.; Strasser, A.; Taniwaki, M.; Maekawa, T. ABT-737 is a useful component of combinatory chemotherapies for chronic myeloid leukaemias with diverse drug-resistance mechanisms. Br. J. Haematol., 2008, 140 (2), 181-190.
127. Kim, K.W.; Moretti, L.; Mitchell, L.R.; Jung, D.K.; Lu, B. Combined Bcl-2/mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model. Clin. Cancer Res., 2009, 15 (19), 6096-6105.
128. High, L.M.; Szymanska, B.; Wilczynska-Kalak, U.; Barber, N.; O'Brien, R.; Khaw, S.L.; Vikstrom, I. B.; Roberts, A.W.; Lock, R.B. The Bcl-2 homology domain 3 mimetic ABT-737 targets the apoptotic machinery in acute lymphoblastic leukemia resulting in synergistic in vitro and in vivo interactions with established drugs. Mol. Pharmacol., 2010, 77 (3), 483-494.
129. Lin, X.; Morgan-Lappe, S.; Huang, X.; Li, L.; Zakula, D.M.; Vernetti, L.A.; Fesik, S.W.; Shen, Y. 'Seed' analysis of off-target siRNAs reveals an essential role of Mcl-1 in resistance to the small-molecule Bcl-2/Bcl-XL inhibitor ABT-737. Oncogene, 2007, 26 (27), 3972-3979.
130. Yecies, D.; Carlson, N.E.; Deng, J.; Letai, A. Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1. Blood, 2010, 115 (16), 3304-3313.
131. Chen, S.; Dai, Y.; Harada, H.; Dent, P.; Grant, S. Mcl-1 downregulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation. Cancer Res., 2007, 67 (2), 782-791.
132. Kang, M.H.; Wan, Z.; Kang, Y.H.; Sposto, R.; Reynolds, C.P., Mechanism of synergy of N-(4-hydroxyphenyl)retinamide and ABT-737 in acute lymphoblastic leukemia cell lines: Mcl-1 inactivation. J. Natl. Cancer Inst., 2008, 100 (8), 580-595.
133. Rudner, J.; Elsaesser, S.J.; Muller, A.C.; Belka, C.; Jendrossek, V. Differential effects of anti-apoptotic Bcl-2 family members Mcl-1, Bcl-2, and Bcl-xL on celecoxib-induced apoptosis. Biochem. Pharmacol., 2010, 79 (1), 10-20.
134. Tse, C.; Shoemaker, A.R.; Adickes, J.; Anderson, M.G.; Chen, J.; Jin, S.; Johnson, E.F.; Marsh, K.C.; Mitten, M.J.; Nimmer, P.; Roberts, L.; Tahir, S.K.; Xiao, Y.; Yang, X.; Zhang, H.; Fesik, S.; Rosenberg, S.H.; Elmore, S.W. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res., 2008, 68 (9), 3421-3428.
135. Lock, R.; Carol, H.; Houghton, P.J.; Morton, C.L.; Kolb, E.A.; Gorlick, R.; Reynolds, C.P.; Maris, J.M.; Keir, S.T.; Wu, J.; Smith, M.A. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr. Blood Cancer, 2008, 50 (6), 1181-1189.
136. Shoemaker, A.R.; Mitten, M.J.; Adickes, J.; Ackler, S.; Refici, M.; Ferguson, D.; Oleksijew, A.; O'Connor, J.M.; Wang, B.; Frost, D.J.; Bauch, J.; Marsh, K.; Tahir, S.K.; Yang, X.; Tse, C.; Fesik, S. W.; Rosenberg, S.H.; Elmore, S.W. Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clin. Cancer Res., 2008, 14 (11), 3268-3277.
137. Ackler, S.; Mitten, M.J.; Foster, K.; Oleksijew, A.; Refici, M.; Tahir, S.K.; Xiao, Y.; Tse, C.; Frost, D.J.; Fesik, S.W.; Rosenberg, S.H.; Elmore, S.W.; Shoemaker, A.R. The Bcl-2 inhibitor ABT- 263 enhances the response of multiple chemotherapeutic regimens in hematologic tumors in vivo. Cancer Chemother. Pharmacol., 2010, 66 (5), 869-880.
138. Gandhi, L.; Camidge, D.R.; Ribeiro de Oliveira, M.; Bonomi, P.; Gandara, D.; Khaira, D.; Hann, C.L.; McKeegan, E.M.; Litvinovich, E.; Hemken, P.M.; Dive, C.; Enschede, S.H.; Nolan, C.; Chiu, Y.L.; Busman, T.; Xiong, H.; Krivoshik, A.P.; Humerickhouse, R.; Shapiro, G.I.; Rudin, C.M. 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 (7), 909-916.
139. Wilson, W.H.; O'Connor, O.A.; Czuczman, M.S.; LaCasce, A.S.; Gerecitano, J.F.; Leonard, J. P.; Tulpule, A.; Dunleavy, K.; Xiong, H.; Chiu, Y.L.; Cui, Y.; Busman, T.; Elmore, S.W.; Rosenberg, S. H.; Krivoshik, A.P.; Enschede, S.H.; Humerickhouse, R.A., 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 (12), 1149-1159
140. Zhang, H.; Nimmer, P.M.; Tahir, S.K.; Chen, J.; Fryer, R.M.; Hahn, K.R.; Iciek, L.A.; Morgan, S. J.; Nasarre, M.C.; Nelson, R.; Preusser, L.C.; Reinhart, G.A.; Smith, M.L.; Rosenberg, S.H.; Elmore, S. W.; Tse, C. Bcl-2 family proteins are essential for platelet survival. Cell Death Differ., 2007, 14 (5), 943-951.
141. Mason, K.D.; Carpinelli, M.R.; Fletcher, J.I.; Collinge, J.E.; Hilton, A.A.; Ellis, S.; Kelly, P.N.; Ekert, P.G.; Metcalf, D.; Roberts, A.W.; Huang, D.C.; Kile, B.T. Programmed anuclear cell death delimits platelet life span. Cell, 2007, 128 (6), 1173-1186.
142. Tahir, S.K.; Wass, J.; Joseph, M.K.; Devanarayan, V.; Hessler, P.; Zhang, H.; Elmore, S.W.; Kroeger, P.E.; Tse, C.; Rosenberg, S.H.; Anderson, M.G. Identification of expression signatures predictive of sensitivity to the Bcl-2 family member inhibitor ABT-263 in small cell lung carcinoma and leukemia/lymphoma cell lines. Mol. Cancer Ther., 2010, 9 (3), 545-557.
143. Li, J.; Viallet, J.; Haura, E.B. A small molecule pan-Bcl-2 family inhibitor, GX15-070, induces apoptosis and enhances cisplatininduced apoptosis in non-small cell lung cancer cells. Cancer Chemother. Pharmacol., 2008, 61 (3), 525-534.
144. Witters, L.M.; Witkoski, A.; Planas-Silva, M.D.; Berger, M.; Viallet, J.; Lipton, A. Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR-HER-2/neu and a Bcl-2 inhibitor. Oncol. Rep., 2007, 17 (2), 465-469.
145. Trudel, S.; Li, Z.H.; Rauw, J.; Tiedemann, R.E.; Wen, X.Y.; Stewart, A.K. Preclinical studies of the pan-Bcl inhibitor obatoclax (GX015- 070) in multiple myeloma. Blood, 2007, 109 (12), 5430-5438.
146. Nguyen, M.; Marcellus, R.C.; Roulston, A.; Watson, M.; Serfass, L.; Murthy Madiraju, S.R.; Goulet, D.; Viallet, J.; Belec, L.; Billot, X.; Acoca, S.; Purisima, E.; Wiegmans, A.; Cluse, L.; Johnstone, R.W.; Beauparlant, P.; Shore, G.C. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc. Natl. Acad. Sci. USA., 2007, 104 (49), 19512-19517.
147. Schimmer, A.D.; O'Brien, S.; Kantarjian, H.; Brandwein, J.; Cheson, B.D.; Minden, M.D.; Yee, K.; Ravandi, F.; Giles, F.; Schuh, A.; Gupta, V.; Andreeff, M.; Koller, C.; Chang, H.; Kamel- Reid, S.; Berger, M.; Viallet, J.; Borthakur, G. A phase I study of the pan bcl-2 family inhibitor obatoclax mesylate in patients with advanced hematologic malignancies. Clin. Cancer Res., 2008, 14 (24), 8295-8301.
148. Hwang, J.J.; Kuruvilla, J.; Mendelson, D.; Pishvaian, M.J.; Deeken, J.F.; Siu, L.L.; Berger, M. S.; Viallet, J.; Marshall, J.L. Phase I dose finding studies of obatoclax (GX15-070), a small molecule pan-BCL-2 family antagonist, in patients with advanced solid tumors or lymphoma. Clin. Cancer Res., 2010, 16 (15), 4038-4045.
149. Vogler, M.; Weber, K.; Dinsdale, D.; Schmitz, I.; Schulze-Osthoff, K.; Dyer, M.J.; Cohen, G.M. Different forms of cell death induced by putative BCL2 inhibitors. Cell Death Differ., 2009, 16 (7), 1030-1039.
150. Jendrossek, V.; Handrick, R.; Belka, C. Celecoxib activates a novel mitochondrial apoptosis signaling pathway. FASEB J., 2003, 17 (11), 1547-1549.
151. Ding, H.; Han, C.; Zhu, J.; Chen, C.S.; D'Ambrosio, S.M. Celecoxib derivatives induce apoptosis via the disruption of mitochondrial membrane potential and activation of caspase 9. Int. J. Cancer, 2005, 113 (5), 803-810.
152. Hsu, A.L.; Ching, T.T.; Wang, D.S.; Song, X.; Rangnekar, V.M.; Chen, C.S. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J. Biol. Chem., 2000, 275 (15), 11397-11403.
153. Johnson, A.J.; Smith, L.L.; Zhu, J.; Heerema, N.A.; Jefferson, S.; Mone, A.; Grever, M.; Chen, C. S.; Byrd, J.C. A novel celecoxib derivative, OSU03012, induces cytotoxicity in primary CLL cells and transformed B-cell lymphoma cell line via a caspase- and Bcl- 2-independent mechanism. Blood, 2005, 105 (6), 2504-2509.
154. Sinha-Datta, U.; Taylor, J.M.; Brown, M.; Nicot, C. Celecoxib disrupts the canonical apoptotic network in HTLV-I cells through activation of Bax and inhibition of PKB/Akt. Apoptosis, 2008, 13 (1), 33-40.
155. Kern, M.A.; Haugg, A.M.; Koch, A.F.; Schilling, T.; Breuhahn, K.; Walczak, H.; Fleischer, B.; Trautwein, C.; Michalski, C.; Schulze- Bergkamen, H.; Friess, H.; Stremmel, W.; Krammer, P.H.; Schirmacher, P.; Muller, M. Cyclooxygenase-2 inhibition induces apoptosis signaling via death receptors and mitochondria in hepatocellular carcinoma. Cancer Res., 2006, 66 (14), 7059-7066.
156. Zhong, Q.; Gao, W.; Du, F.; Wang, X., Mule/ARF-BP1, a BH3- only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell 2005, 121 (7), 1085-1095.
157. Pyrko, P.; Kardosh, A.; Liu, Y. T.; Soriano, N.; Xiong, W.; Chow, R. H.; Uddin, J.; Petasis, N. A.; Mircheff, A.K.; Farley, R.A.; Louie, S.G.; Chen, T.C.; Schonthal, A.H. Calcium-activated endoplasmic reticulum stress as a major component of tumor cell death induced by 2,5-dimethyl-celecoxib, a non-coxib analogue of celecoxib. Mol. Cancer Ther., 2007, 6 (4), 1262-1275.
158. Lin, M.T.; Lee, R.C.; Yang, P.C.; Ho, F.M.; Kuo, M.L. Cyclooxygenase-2 inducing Mcl-1-dependent survival mechanism in human lung adenocarcinoma CL1.0 cells. Involvement of phosphatidylinositol 3-kinase/Akt pathway. J. Biol. Chem., 2001, 276 (52), 48997-49002.
159. Komatsu, K.; Buchanan, F.G.; Katkuri, S.; Morrow, J.D.; Inoue, H.; Otaka, M.; Watanabe, S.; DuBois, R.N. Oncogenic potential of MEK1 in rat intestinal epithelial cells is mediated via cyclooxygenase-2. Gastroenterology 2005, 129 (2), 577-590.
160. Manion, M.K.; O'Neill, J.W.; Giedt, C.D.; Kim, K.M.; Zhang, K.Y.; Hockenbery, D.M. Bcl-XL mutations suppress cellular sensitivity to antimycin A. J. Biol. Chem., 2004, 279 (3), 2159-2165.
161. Schwartz, P.S.; Manion, M.K.; Emerson, C.B.; Fry, J.S.; Schulz, C.M.; Sweet, I.R.; Hockenbery, D. M., 2-Methoxy antimycin reveals a unique mechanism for Bcl-x(L) inhibition. Mol. Cancer Ther., 2007, 6 (7), 2073-2080.
162. Han, Y.H.; Cao, X.; Lin, B.; Lin, F.; Kolluri, S.K.; Stebbins, J.; Reed, J.C.; Dawson, M.I.; Zhang, X.K. Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt. Oncogene, 2006, 25 (21), 2974-2986.
163. Luciano, F.; Krajewska, M.; Ortiz-Rubio, P.; Krajewski, S.; Zhai, D.; Faustin, B.; Bruey, J. M.; Bailly-Maitre, B.; Lichtenstein, A.; Kolluri, S.K.; Satterthwait, A.C.; Zhang, X.K.; Reed, J.C. Nur77 converts phenotype of Bcl-B, an antiapoptotic protein expressed in plasma cells and myeloma. Blood, 2007, 109 (9), 3849-3855.
164. Lomonosova, E.; Chinnadurai, G. BH3-only proteins in apoptosis and beyond: an overview. Oncogene, 2008, 27 Suppl 1, S2-19.
165. Shimizu, S.; Kanaseki, T.; Mizushima, N.; Mizuta, T.; Arakawa- Kobayashi, S.; Thompson, C.B.; Tsujimoto, Y. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat. Cell Biol., 2004, 6 (12), 1221-1228.
166. Oberstein, A.; Jeffrey, P.D.; Shi, Y. Crystal structure of the Bcl- XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein. J. Biol. Chem., 2007, 282 (17), 13123-13132.
167. Maiuri, M.C.; Le Toumelin, G.; Criollo, A.; Rain, J.C.; Gautier, F.; Juin, P.; Tasdemir, E.; Pierron, G.; Troulinaki, K.; Tavernarakis, N.; Hickman, J.A.; Geneste, O.; Kroemer, G. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. Embo. J. 2007, 26 (10), 2527-2539.