Apoptosis: Mechanisms and relevance in cancer

Annals of Hematology

Volumn 84, Issue 10, 2005, Pages 627-639

  Vermeulen, Katrien ^a   Van Bockstaele, Dirk R ^a   Berneman, Zwi N ^a  

^a ANTWERP UNIVERSITY HOSPITAL   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 6 BROMO 4 (1 CYANO 2 ETHOXY 2 OXOETHYL) 4H CHROMENE 3 CARBOXYLIC ACID ETHYL ESTER; ANTIMYCIN A1; ANTISENSE OLIGONUCLEOTIDE; APOPTOSOME; BENZYLOXYCARBONYLVALYLALANYLASPARTYL FLUOROMETHYL KETONE; BH3I 1; BORTEZOMIB; CASPASE; CASPASE INHIBITOR; DEATH RECEPTOR; DEATH RECEPTOR 4 ANTIBODY; EPIGALLOCATECHIN DERIVATIVE; ESTRADIOL 3 METHYL ETHER; ETOPOSIDE; GELDANAMYCIN; GOSSYPOL; LONIDAMINE; MONOCLONAL ANTIBODY; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE; OBLIMERSEN; PROTEIN BAX; PROTEIN BCL 2; PROTEIN INHIBITOR; ROSCOVITINE; SECOND MITOCHONDRIAL ACTIVATOR OF CASPASE; SURVIVIN; THEAFLAVIN; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG; UNINDEXED DRUG; X LINKED INHIBITOR OF APOPTOSIS; Z VAD FMK;

ACUTE GRANULOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BREAST CANCER; CANCER; CARCINOGENESIS; CELL DEATH; CELL PROLIFERATION; CHROMOSOME TRANSLOCATION; CLINICAL TRIAL; COLORECTAL CANCER; CYTOSOL; DRUG PROTEIN BINDING; ENDOPLASMIC RETICULUM; ENZYME ACTIVATION; GENE MUTATION; GENE OVEREXPRESSION; HOMEOSTASIS; HUMAN; LUNG NON SMALL CELL CANCER; LYMPHATIC LEUKEMIA; LYMPHOPROLIFERATIVE DISEASE; MITOCHONDRION; MORPHOLOGY; MUCOSA ASSOCIATED LYMPHOID TISSUE LYMPHOMA; MULTIPLE MYELOMA; NECROSIS; NONHODGKIN LYMPHOMA; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SECRETION; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TUMOR SUPPRESSOR GENE;

ANIMALS; ANTIGENS, CD95; APOPTOSIS; CASPASES; CHROMATIN ASSEMBLY AND DISASSEMBLY; DNA FRAGMENTATION; ENZYME ACTIVATION; FETAL DEVELOPMENT; HOMEOSTASIS; HUMANS; MITOCHONDRIA; NEOPLASMS; RECEPTORS, TUMOR NECROSIS FACTOR, TYPE I; SIGNAL TRANSDUCTION;

EID: 27644542306     PISSN: 09395555     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00277-005-1065-x     Document Type: Review

References (215)

1. Wyllie AH, Kerr JF, Currie AR (1980) Cell death: The significance of apoptosis. Int Rev Cytol 68:251-306 7014501
2. Farber JL, El Mofty SK (1975) The biochemical pathology of liver cell necrosis. Am J Pathol 81:237-250 1180333
3. Uchiyama Y (1995) Apoptosis: The history and trends of its studies. Arch Histol Cytol 58:127-137 7576865
4. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239-257 4561027
5. Yuan J (1996) Evolutionary conservation of a genetic pathway of programmed cell death. J Cell Biochem 60:4-11 8825409
6. Schittny JC, Djonov V, Fine A, Burri PH (1998) Programmed cell death contributes to postnatal lung development. Am J Respir Cell Mol Biol 18:786-793 9618383
7. Scavo LM, Ertsey R, Chapin CJ, Allen L, Kitterman JA (1998) Apoptosis in the development of rat and human fetal lungs. Am J Respir Cell Mol Biol 18:21-31 9448042
8. Green DR, Martin SJ (1995) The killer and the executioner: How apoptosis controls malignancy. Curr Opin Immunol 7:694-703 8573314
9. Liebermann DA, Hoffman B, Steinman RA (1995) Molecular controls of growth arrest and apoptosis: P53-dependent and independent pathways. Oncogene 11:199-210 7624128
10. Shibata S, Kyuwa S, Lee SK, Toyoda Y, Goto N (1994) Apoptosis induced in mouse hepatitis virus-infected cells by a virus-specific CD8+ cytotoxic T-lymphocyte clone. J Virol 68:7540-7545 7933139
11. Nicholson DW, Thornberry NA (1997) Caspases: Killer proteases. Trends Biochem Sci 22:299-306 9270303
12. Thornberry NA, Lazebnik Y (1998) Caspases: Enemies within. Science 281:1312-1316 9721091
13. Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia CM, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT, Nicholson DW (1997) A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem 272:17907-17911 9218414
14. Earnshaw WC, Martins LM, Kaufmann SH (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68:383-424 10872455
15. Duriez PJ, Shah GM (1997) Cleavage of poly(ADP-ribose) polymerase: A sensitive parameter to study cell death. Biochem Cell Biol 75:337-349 9493956
16. Sakahira H, Enari M, Nagata S (1998) Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 391:96-99 9422513
17. Liu X, Zou H, Slaughter C, Wang X (1997) DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 89:175-184 9108473
18. Orth K, Chinnaiyan AM, Garg M, Froelich CJ, Dixit VM (1996) The CED-3/ ICE-like protease Mch2 is activated during apoptosis and cleaves the death substrate lamin A. J Biol Chem 271:16443-16446 8663580
19. Mashima T, Naito M, Fujita N, Noguchi K, Tsuruo T (1995) Identification of actin as a substrate of ICE and an ICE-like protease and involvement of an ICE-like protease but not ICE in VP-16-induced U937 apoptosis. Biochem Biophys Res Commun 217:1185-1192 8554575
20. Martin SJ, O'Brien GA, Nishioka WK, McGahon AJ, Mahboubi A, Saido TC, Green DR (1995) Proteolysis of fodrin (non-erythroid spectrin) during apoptosis. J Biol Chem 270:6425-6428 7534762
21. Song Q, Lees-Miller SP, Kumar S, Zhang Z, Chan DW, Smith GC, Jackson SP, Alnemri ES, Litwack G, Khanna KK, Lavin MF (1996) DNA-dependent protein kinase catalytic subunit: A target for an ICE-like protease in apoptosis. EMBO J 15:3238-3246 8670824
22. Widmann C, Gibson S, Johnson GL (1998) Caspase-dependent cleavage of signaling proteins during apoptosis. A turn-off mechanism for anti-apoptotic signals. J Biol Chem 273:7141-7147 9507028
23. Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770-776 11048727
24. Barkett M, Xue D, Horvitz HR, Gilmore TD (1997) Phosphorylation of IkappaB-alpha inhibits its cleavage by caspase CPP32 in vitro. J Biol Chem 272:29419-29422 9367996
25. Tan X, Martin SJ, Green DR, Wang JYJ (1997) Degradation of retinoblastoma protein in tumor necrosis factor- and CD95-induced cell death. J Biol Chem 272:9613-9616 9092486
26. Grandgirard D, Studer E, Monney L, Belser T, Fellay I, Borner C, Michel MR (1998) Alphaviruses induce apoptosis in Bcl-2-overexpressing cells: evidence for a caspase-mediated, proteolytic inactivation of Bcl-2. EMBO J 17:1268-1278 9482724
27. Clem RJ, Cheng EH, Karp CL, Kirsch DG, Ueno K, Takahashi A, Kastan MB, Griffin DE, Earnshaw WC, Veliuona MA, Hardwick JM (1998) Modulation of cell death by Bcl-XL through caspase interaction. Proc Natl Acad Sci U S A 95:554-559 9435230
28. Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491-501 9727492
29. Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J et al (1992) A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356:768-774 1574116
30. Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A (1996) Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 271:12687-12690 8663110
31. Smith CA, Farrah T, Goodwin RG (1994) The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death. Cell 76:959-962 8137429
32. Ashkenazi A, Dixit VM (1998) Death receptors: Signaling and modulation. Science 281:1305-1308 9721089
33. Boldin MP, Mett IL, Varfolomeev EE, Chumakov I, Shemer AY, Camonis JH, Wallach D (1995) Self-association of the 'death domains' of the p55 tumor necrosis factor (TNF) receptor and Fas/APO1 prompts signaling for TNF and Fas/APO1 effects. J Biol Chem 270:387-391 7529234
34. Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM (1995) FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81:505-512 7538907
35. Nagata S (1997) Apoptosis by death factor. Cell 88:355-365 9039262
36. Medema JP, Scaffidi C, Kischkel FC, Shevchenko A, Mann M, Krammer PH, Peter ME (1997) FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J 16:2794-2804 9184224
37. Stennicke HR, Jurgensmeier JM, Shin H, Deveraux Q, Wolf BB, Yang X, Zhou Q, Ellerby HM, Ellerby LM, Bredesen D, Green DR, Reed JC, Froelich CJ, Salvesen GS (1998) Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem 273:27084-27090 9765224
38. Hsu H, Shu HB, Pan MG, Goeddel DV (1996) TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299-308 8565075
39. Whiteside ST, Israel A (1997) I kappa B proteins: Structure, function and regulation. Semin Cancer Biol 8:75-82 9299585
40. Duan H, Dixit VM (1997) RAIDD is a new 'death' adaptor molecule. Nature 385:86-89 8985253
41. Ahmad M, Srinivasula SM, Wang L, Talanian RV, Litwack G, Fernandes AT, Alnemri ES (1997) CRADD, a novel human apoptotic adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting protein RIP. Cancer Res 57:615-619 9044836
42. Sheikh MS, Fornace AJ Jr (2000) Death and decoy receptors and p53-mediated apoptosis. Leukemia 14:1509-1513 10942251
43. Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90:405-413 9267021
44. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/ caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479-489 9390557
45. Festjens N, van Gurp M, Van Loo G, Saelens X, Vandenabeele P (2004) Bcl-2 family members as sentinels of cellular integrity and role of mitochondrial intermembrane space proteins in apoptotic cell death. Acta Haematol 111:7-27 14646342
46. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658-662 15800627
47. Szewczyk A, Wojtczak L (2002) Mitochondria as a pharmacological target. Pharmacol Rev 54:101-127 11870261
48. Adams JM, Cory S (1998) The Bcl-2 protein family: Arbiters of cell survival. Science 281:1322-1326 9735050
49. Gross A, McDonnell JM, Korsmeyer SJ (1999) Bcl-2 family members and the mitochondria in apoptosis. Genes Dev 13:1899-1911 10444588
50. Minn AJ, Swain RE, Ma A, Thompson CB (1998) Recent progress on the regulation of apoptosis by Bcl-2 family members. Adv Immunol 70:245-279 9755339
51. Kelekar A, Thompson CB (1998) Bcl-2-family proteins: The role of the BH3 domain in apoptosis. Trends Cell Biol 8:324-330 9704409
52. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288:1053-1058 10807576
53. Guo B, Godzik A, Reed JC (2001) Bcl-G, a novel pro-apoptotic member of Bcl-2 family. J Biol Chem 276:2780-2785 11054413
54. Ke N, Godzik A, Reed JC (2001) Bcl-B, a novel Bcl-2 family member that differentially binds and regulates Bax and Bak. J Biol Chem 276:12481-12484 11278245
55. Shinoe T, Wanaka A, Nikaido T, Kanazawa K, Shimizu J, Imaizumi K, Kanazawa I (2001) Upregulation of the pro-apoptotic BH3-only peptide harakiri in spinal neurons of amyotrophic lateral sclerosis patients. Neurosci Lett 313:153-157 11682150
56. Wu X, Deng Y (2002) Bax and BH3-domain-only proteins in p53-mediated apoptosis. Front Biosci 7:151-156
57. Farooq M, Kim Y, Im S, Chung E, Hwang S, Sohn M, Kim M, Kim J (2001) Cloning of BNIP3h, a member of proapoptotic BNIP3 family genes. Exp Mol Med 33:169-173 11642554
58. Inohara N, Ekhterae D, Garcia I, Carrio R, Merino J, Merry A, Chen S, Nunez G (1998) Mtd, a novel Bcl-2 family member activates apoptosis in the absence of heterodimerization with Bcl-2 and Bcl-XL. J Biol Chem 273:8705-8710 9535847
59. Kuwana T, Newmeyer DD (2003) Bcl-2-family proteins and the role of mitochondria in apoptosis. Curr Opin Cell Biol 15:691-699 14644193
60. Reed JC (1996) Mechanisms of Bcl-2 family protein function and dysfunction in health and disease. Behring Inst Mitt 97:72-100 8950468
61. Burlacu A (2003) Regulation of apoptosis by Bcl-2 family proteins. J Cell Mol Med 7:249-257 14594549
62. Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (2005) Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell 17:393-403 15694340
63. Mignotte B, Vayssiere JL (1998) Mitochondria and apoptosis. Eur J Biochem 252:1-15 9523706
64. Ito T, Deng X, Carr B, May WS (1997) Bcl-2 phosphorylation required for anti-apoptosis function. J Biol Chem 272:11671-11673 9115213
65. Blagosklonny MV (2001) Unwinding the loop of Bcl-2 phosphorylation. Leukemia 15:869-874 11417471
66. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Brenner C, Larochette N, Prevost MC, Alzari PM, Kroemer G (1999) Mitochondrial release of caspase-2 and -9 during the apoptotic process. J Exp Med 189:381-394 9892620
67. Mancini M, Nicholson DW, Roy S, Thornberry NA, Peterson EP, Casciola-Rosen LA, Rosen A (1998) The caspase-3 precursor has a cytosolic and mitochondrial distribution: Implications for apoptotic signaling. J Cell Biol 140:1485-1495 9508780
68. Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33-42 10929711
69. Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ, Vaux DL (2000) Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102:43-53 10929712
70. Van Loo G, van Gurp M, Depuydt B, Srinivasula SM, Rodriguez I, Alnemri ES, Gevaert K, Vandekerckhove J, Declercq W, Vandenabeele P (2002) The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ 9:20-26 11803371
71. Van Loo G, Demol H, van Gurp M, Hoorelbeke B, Schotte P, Beyaert R, Zhivotovsky B, Gevaert K, Declercq W, Vandekerckhove J, Vandenabeele P (2002) A matrix-assisted laser desorption ionization post-source decay (MALDI-PSD) analysis of proteins released from isolated liver mitochondria treated with recombinant truncated Bid. Cell Death Differ 9:301-308 11859412
72. Hegde R, Srinivasula SM, Zhang Z, Wassell R, Mukattash R, Cilenti L, DuBois G, Lazebnik Y, Zervos AS, Fernandes-Alnemri T, Alnemri ES (2002) Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem 277:432-438 11606597
73. Li LY, Luo X, Wang X (2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95-99 11452314
74. Luo X, Budihardjo I, Zou H, Slaughter C, Wang X (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94:481-490 9727491
75. Desagher S, Osen-Sand A, Nichols A, Eskes R, Montessuit S, Laupher S, Maundrell K, Antonsson B, Martinou J (1999) Bid-induced conformational change of Bax is reponsible for mitochondrial cytochrome c release during apoptosis. J Cell Biol 144:891-901 10085289
76. Zamzami N, El Hamel C, Maisse C, Brenner C, Munoz-Pinedo C, Belzacq AS, Costantini P, Vieira H, Loeffler M, Molle G, Kroemer G (2000) Bid acts on the permeability transition pore complex to induce apoptosis. Oncogene 19:6342-6350 11175349
77. Jaattela M (2004) Multiple cell death pathways as regulators of tumour initiation and progression. Oncogene 23:2746-2756 15077138
78. Herr I, Debatin KM (2001) Cellular stress response and apoptosis in cancer therapy. Blood 98:2603-2614 11675328
79. Breckenridge DG, Germain M, Mathai JP, Nguyen M, Shore GC (2003) Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 22:8608-8618 14634622
80. Ferri KF, Kroemer G (2001) Organelle-specific initiation of cell death pathways. Nat Cell Biol 3:E255-E263 11715037
81. Momoi T (2004) Caspases involved in ER stress-mediated cell death. J Chem Neuroanat 28:101-105 15363495
82. Kadowaki H, Nishitoh H, Ichijo H (2004) Survival and apoptosis signals in ER stress: The role of protein kinases. J Chem Neuroanat 28:93-100 15363494
83. Goll DE, Thompson VF, Li H, Wei W, Cong J (2003) The calpain system. Physiol Rev 83:731-801 12843408
84. Ng FW, Nguyen M, Kwan T, Branton PE, Nicholson DW, Cromlish JA, Shore GC (1997) p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum. J Cell Biol 139:327-338 9334338
85. Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer JL, Schroter M, Scaffidi C, Krammer PH, Peter ME, Tschopp J (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386:517-521 9087414
86. Hu S, Vincenz C, Ni J, Gentz R, Dixit VM (1997) I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1 and CD-95-induced apoptosis. J Biol Chem 272:17255-17257 9211860
87. Srinivasula SM, Ahmad M, Ottilie S, Bullrich F, Banks S, Wang Y, Fernandes AT, Croce CM, Litwack G, Tomaselli KJ, Armstrong RC, Alnemri ES (1997) FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis. J Biol Chem 272:18542-18545 9228018
88. Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J (1997) Inhibition of death receptor signals by cellular FLIP [see comments]. Nature 388:190-195 9217161
89. Uren AG, Coulson EJ, Vaux DL (1998) Conservation of baculovirus inhibitor of apoptosis repeat proteins (BIRPs) in viruses, nematodes, vertebrates and yeast. Trends Biochem Sci 23:159-162 9612077
90. Liston P, Roy N, Tamai K, Lefebvre C, Baird S, Cherton HG, Farahani R, McLean M, Ikeda JE, MacKenzie A, Korneluk RG (1996) Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 379:349-353 8552191
91. Duckett CS, Nava VE, Gedrich RW, Clem RJ, Van Dongen JL, Gilfillan MC, Shiels H, Hardwick JM, Thompson CB (1996) A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J 15:2685-2694 8654366
92. Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:917-921 917-921 9256286
93. Kasof GM, Gomes BC (2001) Livin, a novel inhibitor of apoptosis protein family member. J Biol Chem 276:3238-3246 11024045
94. Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388:300-304 9230442
95. Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J 16:6914-6925 9384571
96. LaCasse E, Baird S, Korneluk R, MacKenzie A (1998) The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 17:3247-3259 9916987
97. Pathan N, Marusawa H, Krajewska M, Matsuzawa S, Kim H, Okada K, Torii S, Kitada S, Krajewski S, Welsh K, Pio F, Godzik A, Reed JC (2001) TUCAN, an antiapoptotic caspase-associated recruitment domain family protein overexpressed in cancer. J Biol Chem 276:32220-32229 11408476
98. Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen GM, Green DR (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2:469-475 10934466
99. Beere HM (2004) 'The stress of dying': The role of heat shock proteins in the regulation of apoptosis. J Cell Sci 117:2641-2651 15169835
100. Sreedhar AS, Csermely P (2004) Heat shock proteins in the regulation of apoptosis: New strategies iA tumor therapy: a comprehensive review. Pharmacol Ther 101:227-257 15031001
101. McCarthy NJ, Whyte MK, Gilbert CS, Evan GI (1997) Inhibition of Ced-3/ ICE-related proteases does not prevent cell death induced by oncogenes, DNA damage, or the Bcl-2 homologue Bak. J Cell Biol 136:215-227 9008715
102. Vermeulen K, Strnad M, Havlicek L, Van Onckelen H, Lenjou M, Nijs G, Van Bockstaele D, Berneman ZN (2002) Plant cytokinin analogues with inhibitory activity on cyclin dependent kinases (CDK) exert their antiproliferative effect through induction of apoptosis initiated by the mitochondrial pathway: Determination by a multiparametric flow cytometric analysis. Exp Hematol 30:1107-1114 12384140
103. Thornberry NA, Peterson EP, Zhao JJ, Howard AD, Griffin PR, Chapman KT (1994) Inactivation of interleukin-1 beta converting enzyme by peptide (acyloxy)methyl ketones. Biochemistry 33:3934-3940 8142397
104. Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309-1312 9721092
105. Xiang J, Chao DT, Korsmeyer SJ (1996) Bax-induced cell death may not require interleukin 1 beta-converting enzyme-like proteases. Proc Natl Acad Sci U S A 93:14559-14563 8962091
106. Vercammen D, Beyaert R, Denecker G, Goossens V, Van Loo G, Declercq W, Grooten J, Fiers W, Vandenabeele P (1998) Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J Exp Med 187:1477-1485 9565639
107. Schulze OK, Krammer PH, Droge W (1994) Divergent signalling via APO-1/ Fas and the TNF receptor, two homologous molecules involved in physiological cell death. EMBO J 13:4587-4596 7523113
108. Cauwels A, Janssen B, Waeytens A, Cuvelier C, Brouckaert P (2003) Caspase inhibition causes hyperacute tumor necrosis factor-induced shock via oxidative stress and phospholipase A2. Nat Immunol 4:387-393 12652297
109. Mathiasen IS, Jaattela M (2002) Triggering caspase-independent cell death to combat cancer. Trends Mol Med 8:212-220 12067630
110. Johnson DE (2000) Noncaspase proteases in apoptosis. Leukemia 14:1695-1703 10995018
111. Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626-629 15286356
112. Leist M, Jaattela M (2001) Four deaths and a funeral: From caspases to alternative mechanisms. Nat Rev Mol Cell Biol 2:589-598 11483992
113. Fadeel B, Orrenius S, Zhivotovsky B (1999) Apoptosis in human disease: A new skin for the old ceremony? Biochem Biophys Res Commun 266:699-717 10603308
114. Joaquin AM, Gollapudi S (2001) Functional decline in aging and disease: a role for apoptosis. J Am Geriatr Soc 49:1234-1240 11559385
115. Granville DJ, Carthy CM, Hunt DW, McManus BM (1998) Apoptosis: Molecular aspects of cell death and disease. Lab Invest 78:893-913 9714178
116. Saikumar P, Dong Z, Mikhailov V, Denton M, Weinberg JM, Venkatachalam MA (1999) Apoptosis: Definition, mechanisms, and relevance to disease. Am J Med 107:489-506 10569305
117. Evan GI, Vousden KH (2001) Proliferation, cell cycle and apoptosis in cancer. Nature 411:342-348 11357141
118. Reed JC, Miyashita T, Takayama S, Wang HG, Sato T, Krajewski S, Aime SC, Bodrug S, Kitada S, Hanada M (1996) BCL-2 family proteins: Regulators of cell death involved in the pathogenesis of cancer and resistance to therapy. J Cell Biochem 60:23-32 8825412
119. Bakhshi A, Jensen JP, Goldman P, Wright JJ, McBride OW, Epstein AL, Korsmeyer SJ (1985) Cloning the chromosomal breakpoint of t(14;18) human lymphomas: Clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell 41:899-906 3924412
120. Tsujimoto Y, Yunis J, Onorato SL, Erikson J, Nowell PC, Croce CM (1984) Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation. Science 224:1403-1406 6610211
121. Kaufmann SH, Karp JE, Svingen PA, Krajewski S, Burke PJ, Gore SD, Reed JC (1998) Elevated expression of the apoptotic regulator Mcl-1 at the time of leukemic relapse. Blood 91:991-1000 9446661
122. Puthier D, Derenne S, Barille S, Moreau P, Harousseau JL, Bataille R, Amiot M (1999) Mcl-1 and Bcl-XL are co-regulated by IL-6 in human myeloma cells. J Cell Biol 97:1235-1239
123. Amarante-Mendes GP, McGahon AJ, Nishioka WK, Afar DE, Witte ON, Green DR (1998) Bcl-2-independent Bcr-Abl-mediated resistance to apoptosis: protection is correlated with up regulation of Bcl-xL. Oncogene 16:1383-1390 9525737
124. Michels J, Johnson PW, Packham G (2005) Mcl-1. Int J Biochem Cell Biol 37:267-271 15474972
125. Rampino N, Yamamoto H, Ionov Y, Li Y, Sawai H, Reed JC, Perucho M (1997) Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 275:967-969 9020077
126. Brimmell M, Mendiola R, Mangion J, Packham G (1998) BAX frameshift mutations in cell lines derived from human haemopoietic malignancies are associated with resistance to apoptosis and microsatellite instability. Oncogene 16:1803-1812 9583678
127. Ong Y, McMullin M, Bailie K, Lappin T, Jones F, Irvine A (2000) High bax expression is a good prognostic indicator in acute myeloid leukaemia. Br J Haematol 111:182-189 11091199
128. Zamzami N, Brenner C, Marzo I, Susin SA, Kroemer G (1998) Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins. Oncogene 16:2265-2282 9619836
129. Miyashita T, Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293-299 7834749
130. Soengas MS, Alarcon RM, Yoshida H, Giaccia AJ, Hakem R, Mak TW, Lowe SW (1999) Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science 284:156-159 10102818
131. Owen-Schaub LB, Zhang W, Cusack JC, Angelo LS, Santee SM, Fujiwara T, Roth JA, Deisseroth AB, Zhang WW, Kruzel E et al (1995) Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol Cell Biol 15:3032-3040 7539102
132. Sheikh MS, Burns TF, Huang Y, Wu GS, Amundson S, Brooks KS, Fornace AJ Jr, el Deiry WS (1998) p53-dependent and -independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alpha. Cancer Res 58:1593-1598 9563466
133. Chipuk JE, Green DR (2004) Cytoplasmic p53: Bax and forward. Cell Cycle 3:429-431 15020844
134. Amundson SA, Myers TG, Fornace AJ Jr (1998) Roles for p53 in growth arrest and apoptosis: Putting on the brakes after genotoxic stress. Oncogene 17:3287-3299 9916991
135. Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323-331 9039259
136. Schwartz D, Rotter V (1998) p53-dependent cell cycle control: Response to genotoxic stress. Semin Cancer Biol 8:325-336 10101798
137. Muller M, Strand S, Hug H, Heinemann EM, Walczak H, Hofmann WJ, Stremmel W, Krammer PH, Galle PR (1997) Drug-induced apoptosis in hepatoma cells is mediated by the CD95 (APO-1/Fas) receptor/ligand system and involves activation of wild-type p53. J Clin Invest 99:403-413 9022073
138. Oren M (1999) Regulation of the p53 tumor suppressor protein. J Biol Chem 274:36031-36034 10593882
139. Srivastava S, Zou ZQ, Pirollo K, Blattner W, Chang EH (1990) Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome [see comments]. Nature 348:747-749 2259385
140. Sherr CJ, Weber JD (2000) The ARF/p53 pathway. Curr Opin Genet Dev 10:94-99 10679383
141. Khanna KK, Jackson SP (2001) DNA double-strand breaks: Signaling, repair and the cancer connection. Nat Genet 27:247-254 11242102
142. Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, Strober W, Lenardo MJ, Puck JM (1995) Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 81:935-946 7540117
143. Tamiya S, Etoh K, Suzushima H, Takatsuki K, Matsuoka M (1998) Mutation of CD95 (Fas/Apo-1) gene in adult T-cell leukemia cells. Blood 91:3935-3942 9573032
144. Beltinger C, Kurz E, Bohler T, Schrappe M, Ludwig WD, Debatin KM (1998) CD95 (APO-1/Fas) mutations in childhood T-lineage acute lymphoblastic leukemia. Blood 91:3943-3951
145. Landowski TH, Qu N, Buyuksal I, Painter JS, Dalton WS (1997) Mutations in the Fas antigen in patients with multiple myeloma. Blood 90:4266-4270 9373236
146. Siegel RM, Chan FK, Chun HJ, Lenardo MJ (2000) The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity. Nat Immunol 1:469-474 11101867
147. Krammer PH (2000) CD95's deadly mission in the immune system. Nature 407:789-795 11048730
148. Wang J, Zheng L, Lobito A, Chan FK, Dale J, Sneller M, Yao X, Puck JM, Straus SE, Lenardo MJ (1999) Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell 98:47-58 10412980
149. Teitz T, Wei T, Valentine MB, Vanin EF, Grenet J, Valentine VA, Behm FG, Look AT, Lahti JM, Kidd VJ (2000) Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nat Med 6:529-535 10802708
150. Soung YH, Lee JW, Kim SY, Jang J, Park YG, Park WS, Nam SW, Lee JY, Yoo NJ, Lee SH (2005) CASPASE-8 gene is inactivated by somatic mutations in gastric carcinomas. Cancer Res 65:815-821 15705878
151. Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC (1998) Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 396:580-584 9859993
152. Li F (2005) Role of survivin and its splice variants in tumorigenesis. Br J Cancer 92:212-216 15611788
153. Tamm I, Kornblau SM, Segall H, Krajewski S, Welsh K, Kitada S, Scudiero DA, Tudor G, Qui YH, Monks A, Andreeff M, Reed JC (2000) Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res 6:1796-1803 10815900
154. Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM (2000) Identification of paracaspases and metacaspases: Two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell 6:961-967 11090634
155. Morgan JA, Yin Y, Borowsky AD, Kuo F, Nourmand N, Koontz JI, Reynolds C, Soreng L, Griffin CA, Graeme-Cook F, Harris NL, Weisenburger D, Pinkus GS, Fletcher JA, Sklar J (1999) Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18. Cancer Res 59:6205-6213 10626814
156. Motegi M, Yonezumi M, Suzuki H, Suzuki R, Hosokawa Y, Hosaka S, Kodera Y, Morishima Y, Nakamura S, Seto M (2000) API2-MALT1 chimeric transcripts involved in mucosa-associated lymphoid tissue type lymphoma predict heterogeneous products. Am J Pathol 156:807-812 10702396
157. Schmitt CA, Lowe SW (1999) Apoptosis and therapy. J Pathol 187:127-137 10341713
158. Martinez-Lorenzo MJ, Gamen S, Etxeberria J, Lasierra P, Larrad L, Pineiro A, Anel A, Naval J, Alava MA (1998) Resistance to apoptosis correlates with a highly proliferative phenotype and loss of Fas and CPP32 (caspase-3) expression in human leukemia cells. Int J Cancer 75:473-481 9455811
159. Campos L, Rouault JP, Sabido O, Oriol P, Roubi N, Vasselon C, Archimbaud E, Magaud JP, Guyotat D (1993) High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy. Blood 81:3091-3096 7684624
160. Simonian PL, Grillot DA, Nunez G (1997) Bcl-2 and Bcl-XL can differentially block chemotherapy-induced cell death. Blood 90:1208-1216 9242554
161. Minn AJ, Rudin CM, Boise LH, Thompson CB (1995) Expression of bcl-xL can confer a multidrug resistance phenotype. Blood 86:1903-1910 7655019
162. Miyashita T, Reed JC (1993) Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood 81:151-157 8417786
163. Kroemer G, Reed JC (2000) Mitochondrial control of cell death. Nat Med 6:513-519 10802706
164. Friesen C, Herr I, Krammer PH, Debatin KM (1996) Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat Med 2:574-577 8616718
165. Friesen C, Fulda S, Debatin KM (1997) Deficient activation of the CD95 (APO-1/Fas) system in drug-resistant cells. Leukemia 11:1833-1841 9369415
166. Fulda S, Sieverts H, Friesen C, Herr I, Debatin KM (1997) The CD95 (APO-1/Fas) system mediates drug-induced apoptosis in neuroblastoma cells. Cancer Res 57:3823-3829 9288794
167. Fulda S, Friesen C, Los M, Scaffidi C, Mier W, Benedict M, Nunez G, Krammer PH, Peter ME, Debatin KM (1997) Betulinic acid triggers CD95 (APO-1/Fas)- and p53-independent apoptosis via activation of caspases in neuroectodermal tumors. Cancer Res 57:4956-4964 9354463
168. Selleri C, Sato T, Del Vecchio L, Luciano L, Barrett AJ, Rotoli B, Young NS, Maciejewski JP (1997) Involvement of Fas-mediated apoptosis in the inhibitory effects of interferon-alpha in chronic myelogenous leukemia. Blood 89:957-964 9028327
169. Min YH, Lee S, Lee JW et al (1996) Expression of FAS antigen in acute myeloid leukemia is associated with therapeutic response to chemotherapy. Br J Haematol 93:928-930 8703827
170. Medema JP, de Jong J, Peltenburg LT, Verdegaal EM, Gorter A, Bres SA, Franken KL, Hahne M, Albar JP, Melief CJ, Offringa R (2001) Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc Natl Acad Sci U S A 98:11515-11520 11562487
171. Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, DeForge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z, Schwall RH (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104:155-162 10411544
172. Pukac L, Kanakaraj P, Humphreys R, Alderson R, Bloom M, Sung C, Riccobene T, Johnson R, Fiscella M, Mahoney A, Carrell J, Boyd E, Yao XT, Zhang L, Zhong L, von Kerczek A, Shepard L, Vaughan T, Edwards B, Dobson C, Salcedo T, Albert V (2005) HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumour types in vitro and in vivo. Br J Cancer 92:1430-1441 15846298
173. Wang JL, Zhang ZJ, Choksi S, Shan S, Lu Z, Croce CM, Alnemri ES, Korngold R, Huang Z (2000) Cell permeable Bcl-2 binding peptides: A chemical approach to apoptosis induction in tumor cells. Cancer Res 60:1498-1502 10749111
174. Lugovskoy AA, Degterev AI, Fahmy AF, Zhou P, Gross JD, Yuan J, Wagner G (2002) A novel approach for characterizing protein ligand complexes: molecular basis for specificity of small-molecule Bcl-2 inhibitors. J Am Chem Soc 124:1234-1240 11841292
175. Wang JL, Liu D, Zhang ZJ, Shan S, Han X, Srinivasula SM, Croce CM, Alnemri ES, Huang Z (2000) Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci U S A 97:7124-7129 10860979
176. Degterev A (2001) Identification of small-molecule inhibitors of interaction between BH3 domain and Bcl-Xl. Nat Cell Biol 3:173-182 11175750
177. Pellecchia M, Reed JC (2004) Inhibition of anti-apoptotic Bcl-2 family proteins by natural polyphenols: New avenues for cancer chemoprevention and chemotherapy. Curr Pharm Des 10:1387-1398 15134489
178. Qiu J, Levin LR, Buck J, Reidenberg MM (2002) Different pathways of cell killing by gossypol enantiomers. Exp Biol Med (Maywood) 227:398-401
179. Leone M, Zhai D, Sareth S, Kitada S, Reed JC, Pellecchia M (2003) Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins. Cancer Res 63:8118-8121 14678963
180. Degterev A, Lugovskoy A, Cardone M, Mulley B, Wagner G, Mitchison T, Yuan J (2001) Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nat Cell Biol 3:173-182 11175750
181. Tzung SP, Kim KM, Basanez G, Giedt CD, Simon J, Zimmerberg J, Zhang KY, Hockenbery DM (2001) Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3. Nat Cell Biol 3:183-191 11175751
182. Raje N, Kumar S, Hideshima T, Roccaro A, Ishitsuka K, Yasui H, Shiraishi N, Chauhan D, Munshi NC, Green SR, Anderson KC (2005) Seliciclib (CYC202 or R-Roscovitine), a small molecule cyclin dependent kinase inhibitor, mediates activity via downregulation of Mcl-1 in multiple myeloma. Blood prepublished online Apr 12
183. Koty PP, Zhang H, Levitt ML (1999) Antisense bcl-2 treatment increases programmed cell death in non-small cell lung cancer cell lines. Lung Cancer 23:115-127 10217615
184. Keith FJ, Bradbury DA, Zhu YM, Russell NH (1995) Inhibition of bcl-2 with antisense oligonucleotides induces apoptosis and increases the sensitivity of AML blasts to Ara-C. Leukemia 9:131-138 7845007
185. Banerjee D (2001) Genasense (Genta Inc). Curr Opin Investig Drugs 2:574-580 11566020
186. Kitada S, Takayama S, De Riel K, Tanaka S, Reed JC (1994) Reversal of chemoresistance of lymphoma cells by antisense-mediated reduction of bcl-2 gene expression. Antisense Res Dev 4:71-79 7950302
187. Webb A, Cunningham D, Cotter F, Clarke PA, di Stefano F, Ross P, Corbo M, Dziewanowska Z (1997) BCL-2 antisense therapy in patients with non-Hodgkin lymphoma. Lancet 349:1137-1141 9113013
188. Flaherty KT, Stevenson JP, O'Dwyer PJ (2001) Antisense therapeutics: lessons from early clinical trials. Curr Opin Oncol 13:499-505 11673691
189. Marcucci G, Byrd JC, Dai G, Klisovic MI, Kourlas PJ, Young DC, Cataland SR, Fisher DB, Lucas D, Chan KK, Porcu P, Lin ZP, Farag SF, Frankel SR, Zwiebel JA, Kraut EH, Balcerzak SP, Bloomfield CD, Grever MR, Caligiuri MA (2003) Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia. Blood 101:425-432 12393493
190. Rudin CM, Kozloff M, Hoffman PC, Edelman MJ, Karnauskas R, Tomek R, Szeto L, Vokes EE (2004) Phase I study of G3139, a bcl-2 antisense oligonucleotide, combined with carboplatin and etoposide in patients with small-cell lung cancer. J Clin Oncol 22:1110-1117 15020613
191. Tai YT, Strobel T, Kufe D, Cannistra SA (1999) In vivo cytotoxicity of ovarian cancer cells through tumor-selective expression of the Bax gene. Cancer Res 59:2121-2126 10232598
192. Grad JM, Cepero E, Boise LH (2001) Mitochondria as targets for established and novel anti-cancer agents. Drug Resist Updat 4:85-91 11512525
193. Costantini P, Jacotot E, Decaudin D, Kroemer G (2000) Mitochondrion as a novel target of anticancer chemotherapy. J Natl Cancer Inst 92:1042-1053 10880547
194. Amadori D, Frassineti GL, De Matteis A, Mustacchi G, Santoro A, Cariello S, Ferrari M, Nascimben O, Nanni O, Lombardi A, Scarpi E, Zoli W (1998) Modulating effect of lonidamine on response to doxorubicin in metastatic breast cancer patients: Results from a multicenter prospective randomized trial. Breast Cancer Res Treat 49:209-217 9776504
195. Dogliotti L, Danese S, Berruti A, Zola P, Buniva T, Bottini A, Richiardi G, Moro G, Farris A, Bau MG, Porcile G (1998) Cisplatin, epirubicin, and lonidamine combination regimen as first-line chemotherapy for metastatic breast cancer: A pilot study. Cancer Chemother Pharmacol 41:333-338 9488603
196. Ianniello GP, De Cataldis G, Comella P, Scarpati MD, Maiorino A, Brancaccio L, Cioffi R, Lombardi A, Carnicelli P, Tinessa V (1996) Cisplatin, epirubicin, and vindesine with or without lonidamine in the treatment of inoperable nonsmall cell lung carcinoma: A multicenter randomized clinical trial. Cancer 78:63-69 8646728
197. Lane PD, Lain S (2002) Therapeutic exploitation of the p53 pathway. Trends Mol Med 8:38-42 11796265
198. Karin M, Cao Y, Greten FR, Li ZW (2002) NF-kappaB in cancer: From innocent bystander to major culprit. Nat Rev Cancer 2:301-310 12001991
199. Rayet B, Gelinas C (1999) Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18:6938-6947 10602468
200. Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro MG (2000) Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase. Nature 403:103-108 10638762
201. Castro AC, Dang LC, Soucy F, Grenier L, Mazdiyasni H, Hottelet M, Parent L, Pien C, Palombella V, Adams J (2003) Novel IKK inhibitors: beta-carbolines. Bioorg Med Chem Lett 13:2419-2422 12824047
202. Kishore N, Sommers C, Mathialagan S, Guzova J, Yao M, Hauser S, Huynh K, Bonar S, Mielke C, Albee L, Weier R, Graneto M, Hanau C, Perry T, Tripp CS (2003) A selective IKK-2 inhibitor blocks NF-kappa B-dependent gene expression in interleukin-1 beta-stimulated synovial fibroblasts. J Biol Chem 278:32861-32871 12813046
203. Dai Y, Pei XY, Rahmani M, Conrad DH, Dent P, Grant S (2004) Interruption of the NF-kappaB pathway by Bay 11-7082 promotes UCN-01-mediated mitochondrial dysfunction and apoptosis in human multiple myeloma cells. Blood 103:2761-2770 14645003
204. Burke JR, Pattoli MA, Gregor KR, Brassil PJ, MacMaster JF, McIntyre KW, Yang X, Iotzova VS, Clarke W, Strnad J, Qiu Y, Zusi FC (2003) BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. J Biol Chem 278:1450-1456 12403772
205. Paramore A, Frantz S (2003) Bortezomib. Nat Rev Drug Discov 2:611-612 12908468
206. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348:2609-2617 12826635
207. Bold RJ, Virudachalam S, McConkey DJ (2001) Chemosensitization of pancreatic cancer by inhibition of the 26S proteasome. J Surg Res 100:11-17 11516199
208. Fahy BN, Schlieman MG, Mortenson MM, Virudachalam S, Bold RJ (2005) Targeting BCL-2 overexpression in various human malignancies through NF-kappaB inhibition by the proteasome inhibitor bortezomib. Cancer Chemother Pharmacol 56:46-54 15791457
209. Nikrad M, Johnson T, Puthalalath H, Coultas L, Adams J, Kraft AS (2005) The proteasome inhibitor bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim. Mol Cancer Ther 4:443-449 15767553
210. Reed JC (2001) Apoptosis-regulating proteins as targets for drug discovery. Trends Mol Med 7:314-319 11425640
211. Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG (2004) A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science 305:1471-1474 15353805
212. Olie RA, Simoes-Wust AP, Baumann B, Leech SH, Fabbro D, Stahel RA, Zangemeister-Wittke U (2000) A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy. Cancer Res 60:2805-2809 10850418
213. Sasaki H, Sheng Y, Kotsuji F, Tsang BK (2000) Down-regulation of X-linked inhibitor of apoptosis protein induces apoptosis in chemoresistant human ovarian cancer cells. Cancer Res 60:5659-5666
214. Blagosklonny MV (2002) Hsp-90-associated oncoproteins: Multiple targets of geldanamycin and its analogs. Leukemia 16:455-462
215. Schmitt CA, Lowe SW (2001) Apoptosis is critical for drug response in vivo. Drug Resist Updat 4:132-134