Drug Resistance Updates
Volume 9, Issue 1 , Pages 19-25 , February 2006

Restoring p53-mediated apoptosis in cancer cells: New opportunities for cancer therapy

  • Qiang Yu

      Affiliations

    • Corresponding Author InformationTel.: +65 6478 8127; fax: +65 6478 9003.

Received 23 February 2006 ,Revised 1 March 2006 ,Accepted 1 March 2006.

References 

  1. Bertheau P, Plassa F, Espie M, Turpin E, de Roquancourt A, Marty M, et al. Effect of mutated TP53 on response of advanced breast cancers to high-dose chemotherapy. Lancet. 2002;360:852–854
  2. Beuvink I, Boulay A, Fumagalli S, Zilbermann F, Ruetz S, O’Reilly T, et al. The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation. Cell. 2005;120:747–759
  3. Bunz F, Fauth C, Speicher MR, Dutriaux A, Sedivy JM, Kinzler KW, et al. Targeted inactivation of p53 in human cells does not result in aneuploidy. Cancer Res. 2002;62:1129–1133
  4. Bunz F, Hwang PM, Torrance C, Waldman T, Zhang Y, Dillehay L, et al. Disruption of p53 in human cancer cells alters the responses to therapeutic agents. J. Clin. Invest. 1999;104:263–269
  5. Bykov VJ, Issaeva N, Selivanova G, Wiman KG. Mutant p53-dependent growth suppression distinguishes PRIMA-1 from known anticancer drugs: a statistical analysis of information in the National Cancer Institute database. Carcinogenesis. 2002;23:2011–2018
  6. Bykov VJ, Issaeva N, Shilov A, Hultcrantz M, Pugacheva E, Chumakov P, et al. Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat. Med. 2002;8:282–288
  7. Bykov VJ, Selivanova G, Wiman KG. Small molecules that reactivate mutant p53. Eur. J. Cancer. 2003;39:1828–1834
  8. Caelles C, Helmberg A, Karin M. p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature. 1994;370:220–223
  9. Carvajal D, Tovar C, Yang H, Vu BT, Heimbrook DC, Vassilev LT. Activation of p53 by MDM2 antagonists can protect proliferating cells from mitotic inhibitors. Cancer Res. 2005;65:1918–1924
  10. Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, et al. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 2004;303:1010–1014
  11. Chipuk JE, Maurer U, Green DR, Schuler M. Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription. Cancer Cell. 2003;4:371–381
  12. Cimoli G, Malacarne D, Ponassi R, Valenti M, Alberti S, Parodi S. Meta-analysis of the role of p53 status in isogenic systems tested for sensitivity to cytotoxic antineoplastic drugs. Biochim. Biophys. Acta. 2004;1705:103–120
  13. Coll-Mulet L, Iglesias-Serret D, Santidrian AF, Cosialls AM, de Frias M, Castano E, et al. MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood. 2006;107:4109–4114
  14. El-Deiry WS. The role of p53 in chemosensitivity and radiosensitivity. Oncogene. 2003;22:7486–7495
  15. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, et al. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75:817–825
  16. Erster S, Mihara M, Kim RH, Petrenko O, Moll UM. In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation. Mol. Cell. Biol. 2004;24:6728–6741
  17. Fan S, Chang JK, Smith ML, Duba D, Fornace , O’Connor PM. Cells lacking CIP1/WAF1 genes exhibit preferential sensitivity to cisplatin and nitrogen mustard. Oncogene. 1997;14:2127–2136
  18. Fan S, Smith ML, Rivet DJ, Duba D, Zhan Q, Kohn KW, et al. Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline. Cancer Res. 1995;55:1649–1654
  19. Gartel AL, Tyner AL. The role of the cyclin-dependent kinase inhibitor p21 in apoptosis. Mol. Cancer Ther. 2002;1:639–649
  20. Gupta M, Fan S, Zhan Q, Kohn KW, O’Connor PM, Pommier Y. Inactivation of p53 increases the cytotoxicity of camptothecin in human colon HCT116 and breast MCF-7 cancer cells. Clin. Cancer Res. 1997;3:1653–1660
  21. Hamaguchi T, Matsuoka Y, Bechberger J, Ohnishi T, Fujita K, Naus CC, et al. Establishment of an apoptosis-sensitive rat mammary carcinoma cell line with a mutation in the DNA-binding region of p53. Cancer Lett. 2006;232:279–288
  22. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993;75:805–816
  23. Haupt Y, Rowan S, Shaulian E, Vousden KH, Oren M. Induction of apoptosis in HeLa cells by trans-activation-deficient p53. Genes Dev. 1995;9:2170–2183
  24. Hawkins DS, Demers GW, Galloway DA. Inactivation of p53 enhances sensitivity to multiple chemotherapeutic agents. Cancer Res. 1996;56:892–898
  25. Huang S, Shu L, Dilling MB, Easton J, Harwood FC, Ichijo H, et al. Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1). Mol. Cell. 2003;11:1491–1501
  26. Ihrie RA, Reczek E, Horner JS, Khachatrian L, Sage J, Jacks T, et al. Perp is a mediator of p53-dependent apoptosis in diverse cell types. Curr. Biol. 2003;13:1985–1990
  27. Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat. Med. 2004;10:1321–1328
  28. Jascur T, Brickner H, Salles-Passador I, Barbier V, El Khissiin A, Smith B, et al. Regulation of p21(WAF1/CIP1) stability by WISp39, a Hsp90 binding TPR protein. Mol. Cell. 2005;17:237–249
  29. Johnson TM, Hammond EM, Giaccia A, Attardi LD. The p53QS transactivation-deficient mutant shows stress-specific apoptotic activity and induces embryonic lethality. Nat. Genet. 2005;37:145–152
  30. Kakudo Y, Shibata H, Otsuka K, Kato S, Ishioka C. Lack of correlation between p53-dependent transcriptional activity and the ability to induce apoptosis among 179 mutant p53s. Cancer Res. 2005;65:2108–2114
  31. Kawasaki M, Nakanishi Y, Kuwano K, Takayama K, Kiyohara C, Hara N. Immunohistochemically detected p53 and P-glycoprotein predict the response to chemotherapy in lung cancer. Eur. J. Cancer. 1998;34:1352–1357
  32. Kawasaki M, Nakanishi Y, Kuwano K, Yatsunami J, Takayama K, Hara N. The utility of p53 immunostaining of transbronchial biopsy specimens of lung cancer: p53 overexpression predicts poor prognosis and chemoresistance in advanced non-small cell lung cancer. Clin. Cancer Res. 1997;3:1195–1200
  33. Khanna KK, Jackson SP. DNA double-strand breaks: signaling, repair and the cancer connection. Nat. Genet. 2001;27:247–254
  34. Kho PS, Wang Z, Zhuang L, Li Y, Chew JL, Ng HH, et al. p53-regulated transcriptional program associated with genotoxic stress-induced apoptosis. J. Biol. Chem. 2004;279:21183–21192
  35. Klein C, Vassilev LT. Targeting the p53-MDM2 interaction to treat cancer. Br. J. Cancer. 2004;91:1415–1419
  36. Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, Chernov MV, et al. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 1999;285:1733–1737
  37. Kralj M, Pavelic J. p21WAF1/CIP1 is more effective than p53 in growth suppression of mouse renal carcinoma cell line Renca in vitro and in vivo. J. Cancer Res. Clin. Oncol. 2003;129:463–471
  38. Lane DP, Lain S. Therapeutic exploitation of the p53 pathway. Trends Mol. Med. 2002;8:S38–S42
  39. Leu JI, Dumont P, Hafey M, Murphy ME, George DL. Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat. Cell Biol. 2004;6:443–450
  40. Liu ZM, Chen GG, Ng EK, Leung WK, Sung JJ, Chung SC. Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells. Oncogene. 2004;23:503–513
  41. Lowe SW, Ruley HE, Jacks T, Housman DE. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 1993;74:957–967
  42. Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature. 1993;362:847–849
  43. Marchenko ND, Zaika A, Moll UM. Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J. Biol. Chem. 2000;275:16202–16212
  44. Mashima T, Tsuruo T. Defects of the apoptotic pathway as therapeutic target against cancer. Drug Resist. Update. 2005;8:339–343
  45. McCurrach ME, Connor TM, Knudson CM, Korsmeyer SJ, Lowe SW. bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis. Proc. Natl. Acad. Sci. (USA). 1997;94:2345–2349
  46. Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, et al. p53 has a direct apoptogenic role at the mitochondria. Mol. Cell. 2003;11:577–590
  47. Moll UM, Zaika A. Nuclear and mitochondrial apoptotic pathways of p53. FEBS Lett. 2001;493:65–69
  48. O’Brate A, Giannakakou P. The importance of p53 location: nuclear or cytoplasmic zip code?. Drug Resist. Update. 2003;6:313–322
  49. O’Connor PM, Jackman J, Bae I, Myers TG, Fan S, Mutoh M, et al. Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents. Cancer Res. 1997;57:4285–4300
  50. Righetti SC, Della Torre G, Pilotti S, Menard S, Ottone F, Colnaghi MI, et al. A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma. Cancer Res. 1996;56:689–693
  51. Rodriguez-Salas N, Palacios J, Moreno G, de Castro J, Gonzalez-Baron M, Gamallo C. Correlation of p53 oncoprotein expression with chemotherapy response in small cell lung carcinomas. Lung Cancer. 2001;34:67–74
  52. Schuler M, Bossy-Wetzel E, Goldstein JC, Fitzgerald P, Green DR. p53 induces apoptosis by caspase activation through mitochondrial cytochrome c release. J. Biol. Chem. 2000;275:7337–7342
  53. Schuler M, Maurer U, Goldstein JC, Breitenbucher F, Hoffarth S, Waterhouse NJ, et al. p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation. Cell Death Differ. 2003;10:451–460
  54. Secchiero P, Barbarotto E, Tiribelli M, Zerbinati C, de Iasio MG, Gonelli A, et al. Functional integrity of the p53-mediated apoptotic pathway induced by the non-genotoxic agent nutlin-3a in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006;107:4122–4129
  55. Seoane J, Le HV, Massague J. Myc suppression of the p21(Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature. 2002;419:729–734
  56. Shibue T, Takeda K, Oda E, Tanaka H, Murasawa H, Takaoka A, et al. Integral role of Noxa in p53-mediated apoptotic response. Genes Dev. 2003;17:2233–2238
  57. Soengas MS, Alarcon RM, Yoshida H, Giaccia AJ, Hakem R, Mak TW, et al. Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science. 1999;284:156–159
  58. Speidel D, Helmbold H, Deppert W. Dissection of transcriptional and non-transcriptional p53 activities in the response to genotoxic stress. Oncogene. 2006;25:940–953
  59. Talos F, Petrenko O, Mena P, Moll UM. Mitochondrially targeted p53 has tumor suppressor activities in vivo. Cancer Res. 2005;65:9971–9981
  60. Tan J, Zhuang L, Leong HS, Iyer NG, Liu ET, Yu Q. Pharmacologic modulation of glycogen synthase kinase-3beta promotes p53-dependent apoptosis through a direct Bax-mediated mitochondrial pathway in colorectal cancer cells. Cancer Res. 2005;65:9012–9020
  61. Tian H, Wittmack EK, Jorgensen TJ. p21WAF1/CIP1 antisense therapy radiosensitizes human colon cancer by converting growth arrest to apoptosis. Cancer Res. 2000;60:679–684
  62. Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, et al. From the cover: small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc. Natl. Acad. Sci. (USA). 2006;103:1888–1893
  63. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004;303:844–848
  64. Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000;408:307–310
  65. Vogt U, Zaczek A, Klinke F, Granetzny A, Bielawski K, Falkiewicz B. p53 gene status in relation to ex vivo chemosensitivity of non-small cell lung cancer. J. Cancer Res. Clin. Oncol. 2002;128:141–147
  66. Vousden KH. Activation of the p53 tumor suppressor protein. Biochim. Biophys. Acta. 2002;1602:47–59
  67. Vousden KH, Lu X. Live or let die: the cell's response to p53. Nat. Rev. Cancer. 2002;2:594–604
  68. Wahl AF, Donaldson KL, Fairchild C, Lee FY, Foster SA, Demers GW, et al. Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat. Med. 1996;2:72–79
  69. Waldman T, Lengauer C, Kinzler KW, Vogelstein B. Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21. Nature. 1996;381:713–716
  70. Wei CL, Wu Q, Vega VB, Chiu KP, Ng P, Zhang T, et al. A global map of p53 transcription-factor binding sites in the human genome. Cell. 2006;124:207–219
  71. Weiss RH. p21Waf1/Cip1 as a therapeutic target in breast and other cancers. Cancer Cell. 2003;4:425–429
  72. Wouters BG, Giaccia AJ, Denko NC, Brown JM. Loss of p21Waf1/Cip1 sensitizes tumors to radiation by an apoptosis-independent mechanism. Cancer Res. 1997;57:4703–4706
  73. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 is a universal inhibitor of cyclin kinases. Nature. 1993;366:701–704
  74. Yang Y, Ludwig RL, Jensen JP, Pierre SA, Medaglia MV, Davydov IV, et al. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell. 2005;7:547–559

PII: S1368-7646(06)00019-7

doi: 10.1016/j.drup.2006.03.001

Drug Resistance Updates
Volume 9, Issue 1 , Pages 19-25 , February 2006

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