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Essentials of Apoptosis pp 581–596Cite as

Apoptosis in Cancer Biology and Cancer Therapeutics

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Abstract

Most anticancer therapies commonly used in the treatment of human cancer, e.g., chemotherapy, γ-irradiation, immunotherapy, or suicide gene therapy, kill tumor cells by triggering cell death pathways including apoptosis in cancer cells. Hence, the failure to activate such pathways may lead to the resistance of cancers to current treatment approaches. A better understanding of the molecular events that regulate apoptosis in cancers and upon cancer therapy provides the basis for a more rational approach to developing molecular targeted therapies in the fight against cancer.

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References

  1. Hengartner MO. The biochemistry of apoptosis. Nature 2000;407:770–6.

    Article  PubMed  CAS  Google Scholar 

  2. Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature 2001;411:342–8.

    Article  PubMed  CAS  Google Scholar 

  3. Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis 2000;21:485–95.

    Article  PubMed  CAS  Google Scholar 

  4. Johnstone RW, Ruefli AA, Lowe SW. Apoptosis: A link between cancer genetics and chemotherapy. Cell 2002;108:153–64.

    Article  PubMed  CAS  Google Scholar 

  5. Fulda S, Debatin KM. Targeting apoptosis pathways in cancer therapy. Curr Cancer Drug Targets 2004;4:569–76.

    Article  PubMed  CAS  Google Scholar 

  6. Makin G, Dive C. Apoptosis and cancer chemotherapy. Trends Cell Biol 2001;11:S22–6.

    PubMed  CAS  Google Scholar 

  7. Degterev A, Boyce M, Yuan J. A decade of caspases. Oncogene 2003;22:8543–67.

    Article  PubMed  CAS  Google Scholar 

  8. Walczak H, Krammer PH. The CD95 (APO-1/Fas) and the TRAIL (APO-2L) apoptosis systems. Exp Cell Res 2000;256:58–66.

    Article  PubMed  CAS  Google Scholar 

  9. Saelens X, Festjens N, Vande Walle L, van Gurp M, van Loo G, Vandenabeele P. Toxic proteins released from mitochondria in cell death. Oncogene 2004;23:2861–74.

    Article  PubMed  CAS  Google Scholar 

  10. Debatin KM, Poncet D, Kroemer G. Chemotherapy: Targeting the mitochondrial cell death pathway. Oncogene 2002;21:8786–803.

    Article  PubMed  CAS  Google Scholar 

  11. Lassus P, Opitz-Araya X, Lazebnik Y. Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization. Science 2002;297:1352–4.

    Article  PubMed  CAS  Google Scholar 

  12. Okada H, Mak TW. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat Rev Cancer 2004;4:592–603.

    Article  PubMed  CAS  Google Scholar 

  13. Kondo Y, Kanzawa T, Sawaya R, Kondo S. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer 2005;5:726–34.

    Article  PubMed  CAS  Google Scholar 

  14. Friesen C, Fulda S, Debatin KM. Deficient activation of the CD95 (APO-1/Fas) system in drug-resistant cells. Leukemia 1997;11:1833–41.

    Article  PubMed  CAS  Google Scholar 

  15. Fulda S, Scaffidi C, Susin SA, et al. Activation of mitochondria and release of mitochondrial apoptogenic factors by betulinic acid. J Biol Chem 1998;273:33942–8.

    Article  PubMed  CAS  Google Scholar 

  16. Jin Z, McDonald ER, 3rd, Dicker DT, El-Deiry WS. Deficient tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem 2004;279:35829–39.

    Article  PubMed  CAS  Google Scholar 

  17. Debatin KM, Stahnke K, Fulda S. Apoptosis in hematological disorders. Semin Cancer Biol 2003;13:149–58.

    Article  PubMed  CAS  Google Scholar 

  18. LeBlanc HN, Ashkenazi A. Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ 2003;10:66–75.

    Article  PubMed  CAS  Google Scholar 

  19. Dechant MJ, Fellenberg J, Scheuerpflug CG, Ewerbeck V, Debatin KM. Mutation analysis of the apoptotic “death-receptors” and the adaptors TRADD and FADD/MORT-1 in osteosarcoma tumor samples and osteosarcoma cell lines. Int J Cancer 2004;109:661–7.

    Article  PubMed  CAS  Google Scholar 

  20. Pai SI, Wu GS, Ozoren N, et al. Rare loss-of-function mutation of a death receptor gene in head and neck cancer. Cancer Res 1998;58:3513–8.

    PubMed  CAS  Google Scholar 

  21. Pitti RM, Marsters SA, Lawrence DA, et al. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 1998;396:699–703.

    Article  PubMed  CAS  Google Scholar 

  22. Roth W, Isenmann S, Nakamura M, et al. Soluble decoy receptor 3 is expressed by malignant gliomas and suppresses CD95 ligand-induced apoptosis and chemotaxis. Cancer Res 2001;61:2759–65.

    PubMed  CAS  Google Scholar 

  23. Sheikh MS, Huang Y, Fernandez-Salas EA, et al. The antiapoptotic decoy receptor TRID/TRAIL-R3 is a p53-regulated DNA damage-inducible gene that is overexpressed in primary tumors of the gastrointestinal tract. Oncogene 1999;18:4153–9.

    Article  PubMed  CAS  Google Scholar 

  24. Petak I, Danam RP, Tillman DM, et al. Hypermethylation of the gene promoter and enhancer region can regulate Fas expression and sensitivity in colon carcinoma. Cell Death Differ 2003;10:211–7.

    Article  PubMed  CAS  Google Scholar 

  25. Van Noesel MM, Van Bezouw S, Salomons GS, et al. Tumor-specific down-regulation of the tumor necrosis factor-related apoptosis-inducing ligand decoy receptors DcR1 and DcR2 is associated with dense promoter hypermethylation. Cancer Res 2002;62:2157–61.

    PubMed  Google Scholar 

  26. Maecker HL, Yun Z, Maecker HT, Giaccia AJ. Epigenetic changes in tumor Fas levels determine immune escape and response to therapy. Cancer Cell 2002;2:139–48.

    Article  PubMed  CAS  Google Scholar 

  27. Hao C, Beguinot F, Condorelli G, et al. Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells. Cancer Res 2001;61:1162–70.

    PubMed  CAS  Google Scholar 

  28. Krueger A, Baumann S, Krammer PH, Kirchhoff S. FLICE-inhibitory proteins: Regulators of death receptor-mediated apoptosis. Mol Cell Biol 2001;21:8247–54.

    Article  PubMed  CAS  Google Scholar 

  29. Fulda S, Meyer E, Debatin KM. Metabolic inhibitors sensitize for CD95 (APO-1/Fas)-induced apoptosis by down-regulating Fas-associated death domain-like interleukin 1-converting enzyme inhibitory protein expression. Cancer Res 2000;60:3947–56.

    PubMed  CAS  Google Scholar 

  30. Longley DB, Wilson TR, McEwan M, et al. c-FLIP inhibits chemotherapy-induced colorectal cancer cell death. Oncogene 2006;25:838–48.

    Article  PubMed  CAS  Google Scholar 

  31. Fulda S, Kufer MU, Meyer E, van Valen F, Dockhorn-Dworniczak B, Debatin KM. Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer. Oncogene 2001;20:5865–77.

    Article  PubMed  CAS  Google Scholar 

  32. Teitz T, Wei T, Valentine MB, et al. Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nat Med 2000;6:529–35.

    Article  PubMed  CAS  Google Scholar 

  33. Hopkins-Donaldson S, Ziegler A, Kurtz S, et al. Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation. Cell Death Differ 2003;10:356–64.

    Article  PubMed  CAS  Google Scholar 

  34. Pingoud-Meier C, Lang D, Janss AJ, et al. Loss of caspase-8 protein expression correlates with unfavorable survival outcome in childhood medulloblastoma. Clin Cancer Res 2003;9:6401–9.

    PubMed  CAS  Google Scholar 

  35. Harada K, Toyooka S, Shivapurkar N, et al. Deregulation of caspase 8 and 10 expression in pediatric tumors and cell lines. Cancer Res 2002;62:5897–901.

    PubMed  CAS  Google Scholar 

  36. van Noesel MM, van Bezouw S, Voute PA, Herman JG, Pieters R, Versteeg R. Clustering of hypermethylated genes in neuroblastoma. Gene Chrom Cancer 2003;38:226–33.

    Article  CAS  Google Scholar 

  37. Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 1984;226:1097–9.

    Article  PubMed  CAS  Google Scholar 

  38. McDonnell TJ, Korsmeyer SJ. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18). Nature 1991;349:254–6.

    Article  PubMed  CAS  Google Scholar 

  39. Traver D, Akashi K, Weissman IL, Lagasse E. Mice defective in two apoptosis pathways in the myeloid lineage develop acute myeloblastic leukemia. Immunity 1998;9:47–57.

    Article  PubMed  CAS  Google Scholar 

  40. Kitada S, Pedersen IM, Schimmer AD, Reed JC. Dysregulation of apoptosis genes in hematopoietic malignancies. Oncogene 2002;21:3459–74.

    Article  PubMed  CAS  Google Scholar 

  41. Rampino N, Yamamoto H, Ionov Y, et al. Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 1997;275:967–9.

    Article  PubMed  CAS  Google Scholar 

  42. Egle A, Harris AW, Bouillet P, Cory S. Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc Natl Acad Sci USA 2004;101:6164–9.

    Article  PubMed  CAS  Google Scholar 

  43. Tagawa H, Karnan S, Suzuki R, et al. Genome-wide array-based CGH for mantle cell lymphoma: Identification of homozygous deletions of the proapoptotic gene BIM. Oncogene 2005;24:1348–58.

    Article  PubMed  CAS  Google Scholar 

  44. Zinkel SS, Ong CC, Ferguson DO, et al. Proapoptotic BID is required for myeloid homeostasis and tumor suppression. Genes Dev 2003;17:229–39.

    Article  PubMed  CAS  Google Scholar 

  45. Soengas MS, Capodieci P, Polsky D, et al. Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature 2001;409:207–11.

    Article  PubMed  CAS  Google Scholar 

  46. Fu W-N, Bertoni F, Kelsey SM, et al. Role of DNA methylation in the suppression of Apaf-1 protein in human leukaemia. Oncogene 2003;22:451–5.

    Article  PubMed  CAS  Google Scholar 

  47. Chakravarti A, Noll E, Black PM, et al. Quantitatively determined survivin expression levels are of prognostic value in human gliomas. J Clin Oncol 2002;20:1063–8.

    Article  PubMed  CAS  Google Scholar 

  48. Tamm I, Kornblau SM, Segall H, et al. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res 2000;6:1796–803.

    PubMed  CAS  Google Scholar 

  49. Byun DS, Cho K, Ryu BK, et al. Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas. Cancer Res 2003;63:7068–75.

    PubMed  CAS  Google Scholar 

  50. Dan HC, Sun M, Kaneko S, et al. Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP). J Biol Chem 2004;279:5405–12.

    Article  PubMed  CAS  Google Scholar 

  51. Dohi T, Okada K, Xia F, et al. An IAP-IAP complex inhibits apoptosis. J Biol Chem 2004;279:34087–90.

    Article  PubMed  CAS  Google Scholar 

  52. Song Z, Yao X, Wu M. Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis. J Biol Chem 2003;278:23130–40.

    Article  PubMed  CAS  Google Scholar 

  53. Velculescu VE, Madden SL, Zhang L, et al. Analysis of human transcriptomes. Nat Genet 1999;23:387–8.

    Article  PubMed  CAS  Google Scholar 

  54. Dierlamm J, Baens M, Wlodarska I, et al. The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas. Blood 1999;93:3601–9.

    PubMed  CAS  Google Scholar 

  55. Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2002;2:420–30.

    Article  PubMed  CAS  Google Scholar 

  56. Ashkenazi A, Pai RC, Fong S, et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 1999;104:155–62.

    Article  PubMed  CAS  Google Scholar 

  57. Lawrence D, Shahrokh Z, Marsters S, et al. Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions. Nat Med 2001;7:383–5.

    Article  PubMed  CAS  Google Scholar 

  58. Nitsch R, Bechmann I, Deisz RA, et al. Human brain-cell death induced by tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL). Lancet 2000;356:827–8.

    Article  PubMed  CAS  Google Scholar 

  59. Jo M, Kim TH, Seol DW, et al. Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand. Nat Med 2000;6:564–7.

    Article  PubMed  CAS  Google Scholar 

  60. Ehrhardt H, Fulda S, Schmid I, Hiscott J, Debatin KM, Jeremias I. TRAIL induced survival and proliferation in cancer cells resistant towards TRAIL-induced apoptosis mediated by NF-kappaB. Oncogene 2003;22:3842–52.

    Article  PubMed  CAS  Google Scholar 

  61. Chuntharapai A, Dodge K, Grimmer K, et al. Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4. J Immunol 2001;166:4891–8.

    PubMed  CAS  Google Scholar 

  62. Ichikawa K, Liu W, Zhao L, et al. Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Nat Med 2001;7:954–60.

    Article  PubMed  CAS  Google Scholar 

  63. Takeda K, Yamaguchi N, Akiba H, et al. Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy. J Exp Med 2004;199:437–48.

    Article  PubMed  CAS  Google Scholar 

  64. Lin T, Huang X, Gu J, et al. Long-term tumor-free survival from treatment with the GFP-TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells. Oncogene 2002;21:8020–8.

    Article  PubMed  CAS  Google Scholar 

  65. Rohn TA, Wagenknecht B, Roth W, et al. CCNU-dependent potentiation of TRAIL/Apo2L-induced apoptosis in human glioma cells is p53-independent but may involve enhanced cytochrome c release. Oncogene 2001;20:4128–37.

    Article  PubMed  CAS  Google Scholar 

  66. Nagane M, Pan G, Weddle JJ, Dixit VM, Cavenee WK, Huang HJ. Increased death receptor 5 expression by chemotherapeutic agents in human gliomas causes synergistic cytotoxicity with tumor necrosis factor-related apoptosis-inducing ligand in vitro and in vivo. Cancer Res 2000;60:847–53.

    PubMed  CAS  Google Scholar 

  67. Gliniak B, Le T. Tumor necrosis factor-related apoptosis-inducing ligand's antitumor activity in vivo is enhanced by the chemotherapeutic agent CPT-11. Cancer Res 1999;59:6153–8.

    PubMed  CAS  Google Scholar 

  68. Keane MM, Rubinstein Y, Cuello M, et al. Inhibition of NF-kappaB activity enhances TRAIL mediated apoptosis in breast cancer cell lines. Breast Cancer Res Treat 2000;64:211–9.

    Article  PubMed  CAS  Google Scholar 

  69. Belka C, Schmid B, Marini P, et al. Sensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL. Oncogene 2001;20:2190–6.

    Article  PubMed  CAS  Google Scholar 

  70. Chinnaiyan AM, Prasad U, Shankar S, et al. Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy. Proc Natl Acad Sci USA 2000;97:1754–9.

    Article  PubMed  CAS  Google Scholar 

  71. Singh TR, Shankar S, Chen X, Asim M, Srivastava RK. Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo. Cancer Res 2003;63:5390–400.

    PubMed  CAS  Google Scholar 

  72. Ray S, Almasan A. Apoptosis induction in prostate cancer cells and xenografts by combined treatment with Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand and CPT-11. Cancer Res 2003;63:4713–23.

    PubMed  CAS  Google Scholar 

  73. Takimoto R, El-Deiry WS. Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding site. Oncogene 2000;19:1735–43.

    Article  PubMed  CAS  Google Scholar 

  74. Meng RD, El-Deiry WS. p53-independent upregulation of KILLER/DR5 TRAIL receptor expression by glucocorticoids and interferon-gamma. Exp Cell Res 2001;262:154–69.

    Article  PubMed  CAS  Google Scholar 

  75. Wang S, El-Deiry WS. Requirement of p53 targets in chemosensitization of colonic carcinoma to death ligand therapy. Proc Natl Acad Sci USA 2003;100:15095–100.

    Article  PubMed  CAS  Google Scholar 

  76. Lacour S, Micheau O, Hammann A, et al. Chemotherapy enhances TNF-related apoptosis-inducing ligand DISC assembly in HT29 human colon cancer cells. Oncogene 2003;22:1807–16.

    Article  PubMed  CAS  Google Scholar 

  77. Tolcher AW, Mita M, Meropol NJ, et al. Phase I pharmacokinetic and biologic correlative study of mapatumumab, a fully human monoclonal antibody with agonist activity to tumor necrosis factor-related apoptosis-inducing ligand receptor-1. J Clin Oncol 2007;25:1390–5.

    Article  PubMed  CAS  Google Scholar 

  78. Patnaik A, Wakelee H, Mita M, et al. HGS-ETR2—A fully human monoclonal antibody to TRAIL-R2: Results of a phase I trial in patients with advanced solid tumors. Proc Am Soc Clin Oncol 42nd Annual Meeting, A 2006;3012.

    Google Scholar 

  79. Herbst RS, Mendolson DS, Ebbinghaus S, et al. A phase I safety and pharmacokinetic (PK) study of recombinant Apo2L/TRAIL, an apoptosis-inducing protein in patients with advanced cancer. J Clin Oncol 2006;24:3013.

    Article  Google Scholar 

  80. Younes A, Aggarwall BB. Clinical implications of the tumor necrosis factor family in benign and malignant hematologic disorders. Cancer 2003;98:458–67.

    Article  PubMed  CAS  Google Scholar 

  81. Chow LQ, Eckhardt SG, Gustafson DL, et al. HGS-ETR1, an antibody targeting TRAIL-R1, in combination with paclitaxel and carboplatin in patients with advanced solid malignancies: Results of a phase 1 and PK study. J Clin Oncol 2006;24:2515.

    Google Scholar 

  82. Mom CH, Sleijfer S, Gietema JA, et al. A phase 1 study of HGS-ETR1, a fully human agonistic monoclonal antibody to the TRAIL-R1 in combination with gemcitabine and cisplatin in subjects with advanced solid malignancies. In: AACR-NCI-EORTC International Conference on Molecular Therapeutics; 2005.

    Google Scholar 

  83. Tolcher AW, Chi K, Kuhn J, et al. A phase II, pharmacokinetic, and biological correlative study of oblimersen sodium and docetaxel in patients with hormone-refractory prostate cancer. Clin Cancer Res 2005;11:3854–61.

    Article  PubMed  CAS  Google Scholar 

  84. Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005;435:677–81.

    Article  PubMed  CAS  Google Scholar 

  85. Konopleva M, Contractor R, Tsao T, et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 2006;10:375–88.

    Article  PubMed  CAS  Google Scholar 

  86. Van Delft MF, Wei AH, Mason KD, et al. 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;10:389–99.

    Article  PubMed  CAS  Google Scholar 

  87. Tahir SK, Yang X, Anderson MG, et al. Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res 2007;67:1176–83.

    Article  PubMed  CAS  Google Scholar 

  88. Chen Q, Gong B, Mahmoud-Ahmed AS, et al. Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma. Blood 2001;98:2183–92.

    Article  PubMed  CAS  Google Scholar 

  89. Lin X, Morgan-Lappe S, Huang X, et al. “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;26:3972–9.

    Article  PubMed  CAS  Google Scholar 

  90. Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2002;2:183–92.

    Article  PubMed  CAS  Google Scholar 

  91. Yang L, Cao Z, Yan H, Wood WC. Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: Implication for cancer specific therapy. Cancer Res 2003;63:6815–24.

    PubMed  CAS  Google Scholar 

  92. Shiozaki EN, Shi Y. Caspases, IAPs and Smac/DIABLO: Mechanisms from structural biology. Trends Biochem Sci 2004;29:486–94.

    Article  PubMed  CAS  Google Scholar 

  93. 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;8:808–15.

    PubMed  CAS  Google Scholar 

  94. Guo F, Nimmanapalli R, Paranawithana S, et al. Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative-(BMS 247550) and Apo-2L/TRAIL-induced apoptosis. Blood 2002;99:3419–26.

    Article  PubMed  CAS  Google Scholar 

  95. Arnt CR, Chiorean MV, Heldebrant MP, Gores GJ, Kaufmann SH. Synthetic Smac/DIABLO peptides enhance the effects of chemotherapeutic agents by binding XIAP and cIAP1 in situ. J Biol Chem 2002;277:44236–43.

    Article  PubMed  CAS  Google Scholar 

  96. Yang L, Mashima T, Sato S, et al. Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: Therapeutic effect of a novel polyarginine-conjugated Smac peptide. Cancer Res 2003;63:831–7.

    PubMed  CAS  Google Scholar 

  97. Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG. A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science 2004;305:1471–4.

    Article  PubMed  CAS  Google Scholar 

  98. Bockbrader KM, Tan M, Sun Y. A small molecule Smac-mimic compound induces apoptosis and sensitizes TRAIL- and etoposide-induced apoptosis in breast cancer cells. Oncogene 2005;24:7381–8.

    Article  PubMed  CAS  Google Scholar 

  99. Sun H, Nikolovska-Coleska Z, Chen J, et al. Structure-based design, synthesis and biochemical testing of novel and potent Smac peptido-mimetics. Bioorg Med Chem Lett 2005;15:793–7.

    Article  PubMed  CAS  Google Scholar 

  100. Sun H, Nikolovska-Coleska Z, Yang CY, et al. Structure-based design of potent, conformationally constrained Smac mimetics. J Am Chem Soc 2004;126:16686–7.

    Article  PubMed  CAS  Google Scholar 

  101. Sun H, Nikolovska-Coleska Z, Yang CY, et al. Structure-based design, synthesis, and evaluation of conformationally constrained mimetics of the second mitochondria-derived activator of caspase that target the X-linked inhibitor of apoptosis protein/caspase-9 interaction site. J Med Chem 2004;47:4147–50.

    Article  PubMed  CAS  Google Scholar 

  102. Zobel K, Wang L, Varfolomeev E, et al. Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs. ACS Chem Biol 2006;1:525–33.

    Article  PubMed  CAS  Google Scholar 

  103. Sun H, Nikolovska-Coleska Z, Lu J, et al. Design, synthesis, and evaluation of a potent, cell-permeable, conformationally constrained second mitochondria derived activator of caspase (Smac) mimetic. J Med Chem 2006;49:7916–20.

    Article  PubMed  CAS  Google Scholar 

  104. Varfolomeev E, Blankenship JW, Wayson SM, et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell 2007;131:669–81.

    Article  PubMed  CAS  Google Scholar 

  105. Vince JE, Wong WW, Khan N, et al. IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis. Cell 2007;131:682–93.

    Article  PubMed  CAS  Google Scholar 

  106. Petersen SL, Wang L, Yalcin-Chin A, et al. Autocrine TNFalpha signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis. Cancer Cell 2007;12:445–56.

    Article  PubMed  CAS  Google Scholar 

  107. Pei Z, Chu L, Zou W, et al. An oncolytic adenoviral vector of Smac increases antitumor activity of TRAIL against HCC in human cells and in mice. Hepatology 2004;39:1371–81.

    Article  PubMed  CAS  Google Scholar 

  108. Okano H, Shiraki K, Inoue H, et al. Over-expression of Smac promotes TRAIL-induced cell death in human hepatocellular carcinoma. Int J Mol Med 2003;12:25–8.

    PubMed  CAS  Google Scholar 

  109. Ng CP, Bonavida B. X-linked inhibitor of apoptosis (XIAP) blocks Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis of prostate cancer cells in the presence of mitochondrial activation: Sensitization by overexpression of second mitochondria-derived activator of caspase/direct IAP-binding protein with low pl (Smac/DIABLO). Mol Cancer Ther 2002;1:1051–8.

    PubMed  CAS  Google Scholar 

  110. Hunter AM, Kottachchi D, Lewis J, Duckett CS, Korneluk RG, Liston P. A novel ubiquitin fusion system bypasses the mitochondria and generates biologically active Smac/DIABLO. J Biol Chem 2003;278:7494–9.

    Article  PubMed  CAS  Google Scholar 

  111. Nikolovska-Coleska Z, Xu L, Hu Z, et al. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. J Med Chem 2004;47:2430–40.

    Article  PubMed  CAS  Google Scholar 

  112. Schimmer AD, Welsh K, Pinilla C, et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 2004;5:25–35.

    Article  PubMed  CAS  Google Scholar 

  113. Wang Z, Cuddy M, Samuel T, et al. Cellular, biochemical, and genetic analysis of mechanism of small molecule IAP inhibitors. J Biol Chem 2004;279:48168–76.

    Article  PubMed  CAS  Google Scholar 

  114. Carter BZ, Gronda M, Wang Z, et al. Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells. Blood 2005;105:4043–50.

    Article  PubMed  CAS  Google Scholar 

  115. LaCasse EC, Kandimalla ER, Winocour P, et al. Application of XIAP antisense to cancer and other proliferative disorders: Development of AEG35156/GEM640. Ann NY Acad Sci 2005;1058:215–34.

    Article  PubMed  CAS  Google Scholar 

  116. LaCasse EC, Cherton-Horvat GG, Hewitt KE, et al. Preclinical characterization of AEG35156/GEM 640, a second-generation antisense oligonucleotide targeting X-linked inhibitor of apoptosis. Clin Cancer Res 2006;12:5231–41.

    Article  PubMed  CAS  Google Scholar 

  117. LaCasse E, Morris S, Ward T, et al. AEG 35156, a XIAP antisense oligonucleotide, suppresses XIAP levels in targeted tissues isolated from pre-clinical models and from patients. In: 97th American Association Cancer Research Annual Meeting. Washington, DC, 2006.

    Google Scholar 

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Acknowledgments

Work in the author’s laboratory is supported by grants from the Deutsche Forschungsgemeinschaft, the Deutsche Krebshilfe, the Bundesministerium für Forschung und Technologie, Wilhelm-Sander-Stiftung, Else-Kröner-Fresenius Stiftung, the European Community, IAP6/18, and the Landesstiftung Baden-Württemberg.

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  1. University Children’s Hospital, Eythstr.24, D-89075 Ulm, Germany

    Simone Fulda

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Correspondence to Simone Fulda .

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    © 2009 Humana Press, a part of Springer Science+Business Media, LLC

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    Fulda, S. (2009). Apoptosis in Cancer Biology and Cancer Therapeutics. In: Dong, Z., Yin, XM. (eds) Essentials of Apoptosis. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-381-7_26

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