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Apoptin Towards Safe and Efficient Anticancer Therapies

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Anticancer Genes

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 818))

Abstract

The chicken anemia virus derived protein apoptin harbors cancer-selective cell killing characteristics, essentially based on phosphorylation-mediated nuclear transfer in cancer cells and efficient cytoplasmic degradation in normal cells. Here, we describe a growing set of preclinical experiments underlying the promises of the anti-cancer potential of apoptin. Various non-replicative oncolytic viral vector systems have revealed the safety and efficacy of apoptin. In addition, apoptin enhanced the oncolytic potential of adenovirus, parvovirus and Newcastle disease virus vectors. Intratumoral injection of attenuated Salmonella typhimurium bacterial strains and plasmid-based systems expressing apoptin resulted in significant tumor regression. In-vitro and in-vivo experiments showed that recombinant membrane-transferring PTD4- or TAT-apoptin proteins have potential as a future anticancer therapeutics. In xenografted hepatoma and melanoma mouse models PTD4-apoptin protein entered both cancer and normal cells, but only killed cancer cells. Combinatorial treatment of PTD4-apoptin with various (chemo)therapeutic compounds revealed an additive or even synergistic effect, reducing the side effects of the single (chemo)therapeutic treatment. Degradable polymeric nanocapsules harboring MBP-apoptin fusion-protein induced tumor-selective cell killing in-vitro and in-vivo and revealed the potential of polymer-apoptin protein vehicles as an anticancer agent.

Besides its direct use as an anticancer therapeutic, apoptin research has also generated novel possibilities for drug design. The nuclear location domains of apoptin are attractive tools for targeting therapeutic compounds into the nucleus of cancer cells. Identification of cancer-related processes targeted by apoptin can potentially generate novel drug targets. Recent breakthroughs important for clinical applications are reported inferring apoptin-based clinical trials as a feasible reality.

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References

  1. Umar A, Dunn BK, Greenwald P (2012) Future directions in cancer prevention. Nat Rev Cancer 12:835–848

    Article  CAS  PubMed  Google Scholar 

  2. Hanahan D, Weinberg RA (2011) The hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  3. Floor SL, Dumont JE, Maenhout C, Raspe E (2012) Hallmarks of cancer: of all cancers, all the time? Trends Mol Med 18:509–515

    Article  CAS  PubMed  Google Scholar 

  4. Johansson C, Schwartz S (2013) Regulation of human papillomavirus gene expression by splicing and polyadenylation. Nat Rev Microbiol 11:239–251

    Article  CAS  PubMed  Google Scholar 

  5. Gjoerup O, Chang Y (2010) Update on human polyomaviruses and cancer. Adv Cancer Rev 106:1–51

    Article  CAS  Google Scholar 

  6. Cheng J, DeCaprio JA, Fluck MM, Schaffhausen BS (2009) Cellular transformation by simian virus 40 and murine polyoma virus T antigens. Semin Cancer Biol 19:218–228

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Russo A, Terrasi M, Agnese V, Santini D, Bazan V (2006) Apoptosis: a relevant tool for anticancer therapy. Ann Oncol S1:115–123

    Google Scholar 

  8. Bouwman P, Jonkers J (2012) The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance. Nat Rev Cancer 12:587–596

    Article  CAS  PubMed  Google Scholar 

  9. Kreuzaler P, Watson CJ (2012) Killing a cancer: what are the alternatives? Nat Rev Cancer 12:411–424

    Article  CAS  PubMed  Google Scholar 

  10. Cleeland CS, Allen JD, Roberts SA, Brell JM, Giralt SA, Khakoo AY, Kirch RA, Kwitkowski VE, Liao Z, Skillings J (2012) Reducing the toxicity of cancer therapy: recognizing needs, taking action. Nat Rev Clin Oncol 9:471–478.

    Article  CAS  PubMed  Google Scholar 

  11. Coleman RE, Rathbone E, Brown JE (2013) Management of cancer treatment-induced bone loss. Nat Rev Rheumatol. epub ahead of print

    Google Scholar 

  12. Pavet V, Portal MM, Moulin JC, Herbrecht R, Gronemeyer H (2011) Towards novel paradigms for cancer therapy. Oncogene 30:1–20

    Article  CAS  PubMed  Google Scholar 

  13. Backendorf C, Noteborn MHM, Tavassoli M (2009) Proteins killing tumor cells. Transworld Research Network

    Google Scholar 

  14. Grimm S, Noteborn MHM (2010) Anticancer genes: inducers of tumour-specific cell death signaling. Trends Mol Med 16:88–96

    Article  CAS  PubMed  Google Scholar 

  15. Murphy AL (1999) Apoptin: nuclear switch triggers cancer cell death. Gene Ther 6:713–714

    Article  CAS  PubMed  Google Scholar 

  16. Pietersen AM, Van der Eb MM, Rademaker HJ, Van den Wollenberg DJ, Rabelink MJ, Kuppen PJ, Van Dierendonck JH, Van Ormondt H, Marsman D, Van de Velde CJ, Van der Eb AJ, Hoeben RC, Noteborn MHM (1999) Specific tumor-cell killing with adenovirus vectors containing the apoptin gene. Gene Ther 6:882–892

    Article  CAS  PubMed  Google Scholar 

  17. Van der Eb MM, Pietersen AM, Speetjens FM, Kuppen PJ, Van de Velde CJ, Noteborn MHM, Hoeben RC (2002) Gene therapy with apoptin induces regression of xenografted human hepatomas. Cancer Gene Ther 9:53–61

    Article  PubMed  Google Scholar 

  18. Pietersen AM, Rutjes SA, Van Tongeren J, Vogels R, Wesseling JG, Noteborn MHM (2004) The tumor-selective viral protein apoptin effectively kills human bilary tract cancer cells. J Mol Med 82:56–63

    Article  CAS  PubMed  Google Scholar 

  19. Li X, Liu Y, Wen Z, Li C, Lu H, Tian M, Jin K, Sun L, Gao P, Yang E, Xu X, Kan S, Wang Z, Wang Y, Jin N (2010) Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo. Mol Cancer 9:10

    Article  PubMed  Google Scholar 

  20. Liu L, Wu W, Zhu G, Liu L, Guan G, Li X, Jin N, Chi B (2012) Therapeutic efficacy of an TERT promoter-driven oncolytic adenovirus that expresses apoptin in gastric carcinoma. Int J Mol Med 30:747–754

    CAS  PubMed  Google Scholar 

  21. Zhang M, Wang J, Li C, Hu N, Wang K, Ji H, He D, Quan C, Li X, Jin N, Li Y (2013) Potent growth-inhibitory effect of a dual cancer-specific oncolytic adenovirus expressing apoptin on prostate carcinoma. Int J Oncol 42:1052–1060

    CAS  PubMed  Google Scholar 

  22. Zhang KJ, Qian J, Wang SB, Yang Y (2012) Targeting gene-viro-therapy with AFP driving apoptin gene shows potent antitumour effecting hepatocarcinoma. J Biomed Sci 9:19–20

    CAS  Google Scholar 

  23. Wu Y, Zhang X, Wang X, Wang L, Hu S, Liu X, Meng S (2012) Apoptin enhances the oncolytic properties of Newcastle disease virus. Intervirology 55:276–286

    Article  PubMed  Google Scholar 

  24. Cornelis JJ, Lang SI, Stroh-Dege AY, Balboni G, Dinsart C, Rommelaere J (2004) Cancer gene therapy through autonomous parvovirus-mediated gene transfer. Curr Gene Ther 4:249–261

    Article  CAS  PubMed  Google Scholar 

  25. Nuesch JP, Lacroix J, Marchini A, Rommelaere J (2012) Molecular pathways: rodent parvoviruses-mechanisms of oncolysis and prospects for clinical cancer treatment. Clin Cancer Res 18:3516–3523

    Article  PubMed  Google Scholar 

  26. Li X, Jin N, Mi Z, Lian Z, Sun L, Li X, Zheng X (2006) Antitumor effects of a recombinant fowlpox virus expressing apoptin in vivo and in vitro. Int J Cancer 119:2948–2957

    Article  CAS  PubMed  Google Scholar 

  27. Pan Y, Fang L, Fan H, Luo R, Zhao Q, Chen H, Xiao S (2010) Antitumor effects of a recombinant pseudotype baculovirus expressing apoptin in vitro and in vivo. Int J Cancer 126:2741–2751

    CAS  PubMed  Google Scholar 

  28. Ma JL, Han SX, Zhao J, Zhang D, Wang L, Li YD, Zhu Q (2012) Systemic delivery of lentivirus-mediated secretable TAT-apoptin eradicates hepatocellular carcinoma xenografts in nude mice. Int J Oncol 41:1013–1020

    CAS  PubMed  Google Scholar 

  29. Peng DJ, Sun J, Wang YZ, Tian J, Zhang Y-H, Noteborn MHM, Qu S (2007) Inhibition of hepatocarcinoma by systemic delivery of apoptin gene via the hepatic asiaglycoprotein receptor. Cancer Gene Ther 14:66–73

    Article  CAS  PubMed  Google Scholar 

  30. Wang C, Zhang Y (2011) Apoptin gene transfer via modified wheat histone H4 facilitates apoptosis of human ovarian cancer cells. Cancer Biother Radiopharm 26:121–126

    Article  CAS  PubMed  Google Scholar 

  31. An S, Nam K, Choi S, Bai CZ, Lee Y, Park JS (2013) Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic. Int J Nanomedicine 8:821–834

    PubMed Central  PubMed  Google Scholar 

  32. Zhang Y-H (2004) Activation of apoptin, the tumor-specific activator viral death effector. Ph.D. thesis, Leiden University, Leiden, The Netherlands, 2004

    Google Scholar 

  33. Guellen L, Paterson H, Gaken J, Meyers M, Farzaneh F, Tavassoli M (2004) TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells. Oncogene 23:1153–1165

    Article  Google Scholar 

  34. Li J, Wang H, Ma Z, Fan W, Li Y, Han B, Zhang Z, Wang J (2012) TAT-apoptin induces apoptosis in the human bladder cancer EJ cell line and regulates Bax, Bcl-2, caspase-3 and surviving expression. Exp Ther Med 3:1033–1038

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Flinterman M, Farzaneh F, Habib N, Malik F, Gaken J, Tavassoli M (2009) Delivery of therapeutic proteins as secretable TAT fusion products. Mol Ther 17:334–342

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Zhao J, Gao P, Xiao W, Fan LQ, Wang FJ, Li SX, Liu JW (2011) A novel human derived cell-penetrating peptide in drug delivery. Mol Biol Rep 38:2649–2656

    Article  CAS  PubMed  Google Scholar 

  37. Sun J, Yan Y, Wang XT, Liu XW, Peng DJ, Wang M, Tian J, Zong YQ, Zhang YH, Noteborn MHM, Qu S (2009) PTD4-apoptin protein therapy inhibits tumor growth in vivo. Int J Cancer 124:2973–2981

    Article  CAS  PubMed  Google Scholar 

  38. Zhao M, Hu B, Gu Z, Joo K-I, Wang P, Tang Y (2013) Degradable polymeric nanocapsule for efficient intracellular delivery of a high molecular weight tumor-selective protein complex. Nano Today 8:11–20

    Article  CAS  Google Scholar 

  39. Jin JL, Gong J, Yin TJ, Lu YJ, Xia JJ, Xie YY, Di Y, Guo JL, Sun J, Noteborn MHM, Qu S (2011) PTD4-apoptin protein and dacarbazine show a synergistic antitumor effect on B16-F1 melanoma in vitro and in vivo. Eur J Pharmacol 654:17–25

    Article  CAS  PubMed  Google Scholar 

  40. Olijslagers SJ, Zhang YH, Backendorf C, Noteborn MHM (2007) Additive cytotoxic effect of apoptin and chemotherapeutic agents paclitaxel and etoposide on human tumour cells. Basic Clin Pharmacol Toxicol 100:127–131

    PubMed  Google Scholar 

  41. Lian H, Jin N, Li X, Mi Z, Zhang J, Sun L, Li X, Zheng H, Li P (2007) Induction of an effective anti-tumor immune response and tumor regression by combined administration of IL-18 and apoptin. Cancer Immunol Immunother 56:181–192

    Article  CAS  PubMed  Google Scholar 

  42. Liu Q, Fu H, Xing R, Tie Y, Zhu J, Sun Z, Zheng X (2008) Survivin knockdown combined with apoptin overexpression inhibits growth significantly. Cancer Biol Ther 7:1053–1060

    Article  CAS  PubMed  Google Scholar 

  43. Panigrini S, Klonisch T, Los M (2008) The art of killing: double stroke with apoptin and survivin as a novel approach in cancer therapy. Cancer Biol Ther 7:1061–1062

    Article  Google Scholar 

  44. Castano AP, Mroz P, Hamblin MR (2006) Photodynamic therapy and anti-tumor immunity. Nat Rev Cancer 6:535–545

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Fang X, Wu P, Li J, Qi L, Tang Y, Jiang W, Zhao S (2012) Combination of apoptin with photodynamic therapy induces nasopharyngeal carcinoma cell death in vitro and in vivo. Oncol Rep 28:2077–2082

    CAS  PubMed  Google Scholar 

  46. Kaliberov SA, Buchsbaum DJ (2012) Chapter seven: cancer treatment with gene therapy and radiation therapy. Adv Cancer Res 115:221–263

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Han SX, Zhu Q, Ma JL, Lv Y, Zhao J, Huang C, Jia X, Ou W, Guo HT (2011) Apoptin sensitizes radiation-induced cell death via classic mitochondrial, caspase and p53-dependent signaling in HepG2 cells. Mol Med Res 4:59–63

    CAS  Google Scholar 

  48. Bolhassani A, Zahedifard F (2012) Therapeutic live vaccines as a potential anticancer therapy. Int J Cancer 131:1733–1743

    Article  CAS  PubMed  Google Scholar 

  49. Gardlik R, Fruehauf JH (2010) Baterial vectors and delivery systems in cancer therapy. IDrugs 13:701–706

    CAS  PubMed  Google Scholar 

  50. Cao HD, Yang YX, Lu L, Liu SN, Wang PL, Tao XH, Wang LJ, Xiang TX (2010) Attenuated Salmonella typhimurium carrying TRAIL and VP3 genes inhibits the growth of gastric cancer cells in vitro and in vivo. Tumorigenesis 96:296–303

    CAS  Google Scholar 

  51. Alvisi G, Poon IK, Jans DA (2006) Tumor-specific nuclear targeting: promises for anti-cancer therapy? Drug Resist Updat 9:40–50

    Article  CAS  PubMed  Google Scholar 

  52. Kuusisto HV, Wagstaff KM, Alvisi G, Jans DA (2008) The C-terminus of apoptin represents a unique tumor cell-enhanced nuclear targeting module. Int J Cancer 123:2965–2969

    Article  CAS  PubMed  Google Scholar 

  53. Wagstaff KM, Jans DA (2009) Nuclear drug delivery to target tumour cells. Eur J Pharmacol 625:174–180

    Article  CAS  PubMed  Google Scholar 

  54. Leliveld SR, Dame RT, Mommaas MA, Koerten HK, Wyman C, Danen-Van Oorschot AAAM, Rohn JL, Noteborn MHM, Abrahams JP (2003) Apoptin protein multimers form distinct higher-order nucleoprotein complexes with DNA. Nucleic Acids Res 31:4805–4813

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Rohn JL, Zhang Y-H, Aalbers RI, Otto N, Den Hertog J, Henriquez NV, Van de Velde CJ, Kuppen PJ, Mumberg D, Donner P, Noteborn MHM (2002) A tumor-specific kinase activity regulates the viral death protein apoptin. J Biol Chem 277:50820–50827

    Article  CAS  PubMed  Google Scholar 

  56. Maddika S, Panigrahi S, Wiechec E, Wesselborg S, Fischer U, Schulze-Osthoff K, Los M (2009) Unscheduled Akt-triggered activation of cyclin-dependent kinase 2 as a key effector mechanism of apoptin’s anticancer toxicity. Mol Cell Biol 29:1235–1248

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Jiang J, Cole D, Westwood N, Macpherson L, Farzaneh F, Mufti G, Tavassoli M, Gaken J (2010) Crucial roles for protein kinase C isoforms in tumor-specific killing by apoptin. Cancer Res 70:7242–7252

    Article  CAS  PubMed  Google Scholar 

  58. Peters MA, Jackson DC, Crabb BS, Browning GF (2002) Chicken anemia virus VP2 is a novel dual specificity protein phosphatase. J Biol Chem 277:39566–39573

    Article  CAS  PubMed  Google Scholar 

  59. Backendorf C, Visser AE, De Boer AG, Zimmerman RME, Visser M, Voskamp P, Zhang Y-H, Noteborn MHM (2008) Apoptin: therapeutic potential of an early sensor of carcinogenic transformation. Annu Rev Pharmacol Toxicol 48:143–169

    Article  CAS  PubMed  Google Scholar 

  60. Zimmerman RME, Peng D, Lanz HL, Zhang Y-H, Danen-Van Oorschot AAAM, Qu S, Backendorf C, Noteborn MHM (2012) PP2A inactivation is a crucial step in triggering apoptin-induced tumor-selective killing. Cell Death Dis 3:e293

    Article  Google Scholar 

  61. Zimmerman RME (2011) Apoptin: oncogenic transformation and tumor-selective apoptosis. Ph.D. thesis, Leiden University, Leiden, The Netherlands

    Google Scholar 

  62. Noteborn MHM (2009) Proteins selectively killing tumour cells. Eur J Pharmacol 625:165–173

    Article  CAS  PubMed  Google Scholar 

  63. Melo JV, Barnes DJ (2007) Chronic myeloid leukemia as a model of disease evolution in human cancer. Nat Rev Cancer 7:441–453

    Article  CAS  PubMed  Google Scholar 

  64. Weisberg E, Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD (2007) Second generation inhibitors of Bcr-Abl for the treatment of imanitib-resistant myeloid leukemia. Nat Rev Cancer 7:345–356

    Article  CAS  PubMed  Google Scholar 

  65. Zhuang SM, Landegent JE, Verschueren CA, Falkenburg JH, van Ormondt H, Van der Eb AJ, Noteborn MHM (1995) Apoptin, a protein encoded by chicken anemia virus, induces cell death in various human hematologic malignant cells in vitro. Leukemia S1:118–120

    Google Scholar 

  66. Panigrahi S, Stetefeld J, Jangamreddy JR, Mandal S, Mandal SK, Los M (2012) Modeling of molecular interaction between apoptin, Bcr-Abl and CrkL: an alternative approach to conventional rational drug design. PLoS One 7:e28395

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Morad SA, Cabot MC (2013) Ceramide-orchestrated signaling in cancer cells. Nat Rev Cancer 13:51–65

    Article  CAS  PubMed  Google Scholar 

  68. Liu X, Elojeimy S, El-Zawahry AM, Hollman DH, Bielawska A, Bielawski J, Rubinchik S, Guo GW, Dong JY, Keane T, Hannun YA, Tavassoli M, Norris JS (2006) Modulation of ceramide metabolism enhances viral protein apoptin’s cytotoxicity in prostate cancer. Mol Ther 14:637–646

    Article  CAS  PubMed  Google Scholar 

  69. Zhang Y-H, Leliveld SR, Kooistra K, Molenaar C, Rohn JL, Tanke HJ, Abrahams JP, Noteborn MHM (2003) Recombinant apoptin multimers kill tumor cells but are nontoxic and epitope-shielded in a normal-cell-specific fashion. Exp Cell Res 289:36–46

    Article  CAS  PubMed  Google Scholar 

  70. Pietersen A (2003) Preclinical studies with apoptin. Ph.D. thesis, Erasmus University, Rotterdam, The Netherlands

    Google Scholar 

  71. Zhang Y-H, Kooistra K, Peng D, Backendorf C, Noteborn MHM (2009) Apoptin senses transformation-related nuclear transfer of SV40 large T antigen. In: Backendorf C, Noteborn MHM, Tavassoli M (eds) Proteins killing tumour cells. Transworld Research Network (Kerala, India), pp 179–190

    Google Scholar 

  72. Lanz HL, Florea BI, Noteborn MHM, Backendorf C (2012a) Development and application of an in-vitro apoptin kinase assay. Anal Biochem 421:68–74

    Article  CAS  PubMed  Google Scholar 

  73. Hu Z, Zhang Z, Doo E, Coux O, Goldberg AL, Liang TJ (1999) Hepatitis B virus X protein is both a substrate and a potential inhibitor of the proteasome. J Virol 73:7231–7240

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Smolders L, Teodoro JG (2011) Targeting the anaphase promoting complex: common pathways for viral infection and cancer therapy. Expert Opin Ther Targets 15:767–780

    Article  CAS  PubMed  Google Scholar 

  75. Bousquet-Dubouch MP, Fabre B, Monsarrat B, Burlet-Schiltz O (2011) Proteomics to study the diversity and dynamics of proteasome complexes from fundamentals to the clinic. Expert Rev Proteomics 8:459–481

    Article  CAS  PubMed  Google Scholar 

  76. Eichhorn PJ, Creyghton MP, Bernards R (2009) Protein phosphatase 2A regulating subunits and cancer. Biochem Biophys Acta 2795:1–15

    Google Scholar 

  77. Sablina AA, Hector M, Colpaert N, Hahn WC (2010) Identification of PP2A complexes and pathways involved in cell transformation. Cancer Res 70:10474–10484

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Yang J, Phiel C (2010) Functions of B56-containing PP2As in major developmental and cancer signaling pathways. Life Sci 87:659–666

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Seshacharyulu P, Pandey P, Datta K, Batra SK (2013) Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer. Cancer Lett. epub ahead of print

    Google Scholar 

  80. Janssens V, Rebollo A (2012) The role and therapeutic potential of Ser/Thr phosphatase PP2A in apoptotic signaling networks in human cancer cells. Curr Mol Med 12:268–287

    Article  CAS  PubMed  Google Scholar 

  81. Wurzenberger C, Gerlich DW (2011) Phosphatases: providing safe passage through mitotic exit. Nat Rev Mol Cell Biol 12:469–482

    Article  CAS  PubMed  Google Scholar 

  82. Kitching R, Li H, Wong MJ, Kanaganayakam S, Kahn H, Seth A (2003) Characterization of a novel human breast cancer associated gene (BCA3) encoding an alternatively spliced proline-rich protein. Biochim Biophys Acta 1625:116–121

    Article  CAS  PubMed  Google Scholar 

  83. Kops GJPL, Weaver BAA, Cleveland DW (2005) On the road of cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5:773–785

    Article  CAS  PubMed  Google Scholar 

  84. Galuzzi L, Vitale I, Abrams JM, Alnemri ES, Baerecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, Gottlieb E, Green DR, Hengartner MO, Kepp O, Knight RA, Kumar S, Lipton SA, Lu X, Madeo F, Malorni W, Mehlen P, Nunez G, Peter ME, Piacentini M, Rubinsztein DC, Shi Y, Simon HU, Vandenabeele P, White E, Yuan J, Zhivotovsky B, Melino G, Kroemer G (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on cell death 2012. Cell Death Differ 19:107–120

    Article  Google Scholar 

  85. Vitale I, Galuzzi L, Castedo M, Kroemer G (2011) Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol 12:385–392

    Article  CAS  PubMed  Google Scholar 

  86. Teodoro JG, Heilman DW, Parker AE, Green MR (2004) The viral protein apoptin associates with the anaphase-promoting complex to induce G2/M arrest and apoptosis in the absence of p53. Genes Dev 18:1952–1957

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Lanz HL, Zimmerman RM, Brouwer J, Noteborn MHM, Backendorf C (2013) Mitotic catastrophe triggered in human cancer cells by the viral protein apoptin. Cell Death Dis 4:e487

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Nguyen LV, Vanner R, Dirks P, Eaves CJ (2012) Cancer stem cells: an evolving concept. Nat Rev Cancer 12:133–143

    CAS  PubMed  Google Scholar 

  89. Greaves M, Maley CC (2012) Clonal evolution in cancer. Nature 481:306–313

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Hombach-Klonisch S, Paranjothy T, Wieches E, Pocar P, Mustafa T, Seifert A, Zahl C, Gerlach KL, Biermann K, Steger K, Hoang-Vu C, Schulze-Osthoff K, Los M (2008) Cancer stem cells as targets for cancer therapy: selected cancers as examples. Arch Immunol Ther Exp (Warsz) 56:165–180

    Article  Google Scholar 

  91. Danen-Van Oorschot AAAM, Fischer DF, Grimbergen JM, Klein B, Zhuang S, Falkenburg JH, Backendorf C, Quax PH, Van der Eb AJ, Noteborn MHM (1997) Apoptin induces apoptosis in human transformed and malignant cells but not in normal cells. Proc Natl Acad Sci 94:5843–5847

    Article  CAS  PubMed  Google Scholar 

  92. Danen-Van Oorschot AAAM, Zhang YH, Leliveld SR, Rohn JL, Seelen MC, Bol MW, Van Zon A, Erkeland SJ, Abrahams JP, Mumberg D, Noteborn MHM (2003) Importance of nuclear localization of apoptin for tumor-specific induction of apoptosis. J Biol Chem 278:27729–27736

    Article  CAS  PubMed  Google Scholar 

  93. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  94. Lanz HL, Suijker J, Noteborn MHM, Backendorf C (2012b) Proteasomal insensitivity of apoptin in tumor cells. Biochem Biophys Res Commun 422:169–173

    Article  CAS  PubMed  Google Scholar 

  95. Mato AR, Feldman T, Goy A (2010) Proteasome inhibition and combination therapy for non-Hodgkin’s lymphoma: from bench to bedside. Oncologist 17:694–707

    Article  Google Scholar 

  96. Olijslagers SJ, Dege AY, Dinsart C, Voorhoeve M, Rommelaere J, Noteborn MHM, Cornelis J (2001) Potentiation of a recombinant oncolytic parvovirus by expression of apoptin. Cancer Gene Ther 8:958–965

    Article  CAS  PubMed  Google Scholar 

  97. Perez de Castro I, Malumbres M (2012) Mitotic stress and chromosomal instability in cancer: the case for TPX2. Genes Cancer 3:721–730

    Article  PubMed Central  PubMed  Google Scholar 

  98. Pipas J (2009) SV40: Cell transformation and tumorigenesis. Virology 384:294–303

    Article  CAS  PubMed  Google Scholar 

  99. Schoop RA, Verdegaal EM, Baatenburg de Jong RJ, Noteborn MHM (2010) Apoptin enhances radiation-induced cell death in poorly responding head and neck squamous cell carcinoma cells. Basic Clin Pharmacol Toxicol 106:130–134

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Biology, Leiden Institute for Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands

    Claude Backendorf

  2. Department of Molecular Genetics, Leiden Institute for Chemistry, Leiden University, Leiden, The Netherlands

    Mathieu H. M. Noteborn

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Correspondence to Claude Backendorf .

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  1. Hammersmith Campus, Imperial College London, London, United Kingdom

    Stefan Grimm

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Backendorf, C., Noteborn, M.H.M. (2014). Apoptin Towards Safe and Efficient Anticancer Therapies. In: Grimm, S. (eds) Anticancer Genes. Advances in Experimental Medicine and Biology, vol 818. Springer, London. https://doi.org/10.1007/978-1-4471-6458-6_3

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