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Abstract

Treatment of cells with clinically relevant exposures to cisplatin (DDP) activates an injury response that eventually induces death via an apoptotic mechanism. The activation of apoptosis involves generation of a signal from a detector that senses the presence of DDP-induced damage, and the integration of this signal with information arriving from receptors on both the cell surface and in the interior of the cell. The ability of the cell to trigger apoptosis appears to be dependent on the integrity of these signal transduction pathways, and on the ratio of various members of the bcl-2 family of proteins and their heterodimerization partners in the cell. The molecular dissection of the signal transduction pathways involved has identified numerous opportunities where pharmacologic intervention may enhance the selectivity of the platinum-containing compounds.

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References

  1. Prestayko AW. Cisplatin: A preclinical overview. In: Prestayko AW, Crooke ST, Carter SK, eds. Cisplatin: Current Status and New Developments. New York: Academic Press, 1980:1–7.

    Google Scholar 

  2. Skipper HE. A review and more quantitative analysis of the results of many internally controlled combination chemotherapy trials carried out over the past 15 years (L1210 and leukemia and P388 leukemia). Southern Res Inst 1979; monograph #2.

    Google Scholar 

  3. Schabel FM, Jr., Skipper HE, Trader MW. Concepts for controlling drug-resistant tumor cells. In: Mouridsen HT, Palshof T, eds. Breast Cancer: Experimental and Clinical Aspects. Oxford: Pergamon Press, 1980:199–212.

    Google Scholar 

  4. Goldie H, Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 1979; 63:1727–1733.

    CAS  PubMed  Google Scholar 

  5. DeMrs R. Resistance of cultured human fibroblasts and other cells to purine analogs in relation to mutagenesis detection. Mutation Res 1974; 14:335.

    Google Scholar 

  6. Barry A, Behnke CA, Eastman A. Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem Pharmacol 1990; 40:2353–2361.

    Article  CAS  PubMed  Google Scholar 

  7. Ormerod G, O’Neill CF, Robertson D, Harrap KR. Cisplatin induces apoptosis in a human ovarian carcinoma cell line without concomitant internucleosomal degradation of DNA. Exp Cell Res 1994; 211:231–237.

    Article  CAS  PubMed  Google Scholar 

  8. Kerr FR, Winterford CM, Harmon BV. Apoptosis: its significance in cancer and cancer therapy. Cancer 1994; 73:2013–2026.

    Article  CAS  PubMed  Google Scholar 

  9. Matzinger. The JAM test. A simple assay for DNA fragmentation and cell death. J Immunol Methods 1991; 145:185–192.

    Article  CAS  PubMed  Google Scholar 

  10. Gorczyca, Gong J, Darzynkiewicz Z. Detection of DNA strand breaks in individual apoptotic cells by the in situ terminal deoxynucleotidyl transferase and nick translation assays. Cancer Res 1993; 53:1945–1951.

    Google Scholar 

  11. Toney H, Donahue BA, Kellert PJ, Bruhn SL, Essigmann JM, Lippard SJ. Isolation of cDNAs encoding a human protein that binds selectively to DNA modified by the anticancer drug cis-diamminedichloroplatinum(II). Proc Natl Acad Sci USA 1989; 86:8328–8332.

    Article  CAS  PubMed  Google Scholar 

  12. Donahue BA, Augot M, Bellon SF, et al. Characterization of a DNA damage-recognition protein from mammalian cells that binds to intrastrand d(GpG) and d(ApG) DNA adducts of the anticancer drug cisplatin. Biochemistry 1990; 29:5872–5880.

    Article  CAS  PubMed  Google Scholar 

  13. Gottliebanya M, Jackson Stephen P. The DNA-Dependent Protein Kinase: Requirement for DNA Ends and Association with Ku Antigen. Cell 1993; 72:131–142.

    Article  Google Scholar 

  14. Andersonarl Carl W. DNA damage and the DNA-activated protein kinase. TIBS 1993; 433–437.

    Google Scholar 

  15. Christen RD, Horn DK, Porter DC, et al. Epidermal growth factor regulates the in vitro sensitivity of human ovarian carcinoma cells to cisplatin. J Clin Invest 1990; 86:1632–1640.

    Article  CAS  PubMed  Google Scholar 

  16. Isonishi S, Jekunen AP, Horn DK, et al. Modulation of cisplatin sensitivity and growth rate of an ovarian carcinoma cell line by bombesin and tumor necrosis factor alpha. J Clin Invest 1992; 90:1436–1442.

    Article  CAS  PubMed  Google Scholar 

  17. Fanhen, Zhen, Baselga Jose, Masui Hideo, Mendelsohn John. Antitumor Effect of Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies plus cis-Diamminedichloroplatinum on Well Established A431 Cell Xenografts. Cancer Res 1993; 53:4637–4642.

    Google Scholar 

  18. Pietras RJ, Fendly BM, Chazin VR, Pegram MD, Howell SB, Slamon DJ. Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. Oncogene 1994; 9:1829–1838.

    CAS  PubMed  Google Scholar 

  19. Isonishi S, Andrews PA, Howell SB. Increased sensitivity to cis-diamminedichloroplatinum(II) in human ovarian carcinoma cells in response to treatment with 12-0-tetradecanoylphorbol-13-acetate. J Biol Chem 1990; 265:3623–3627.

    CAS  PubMed  Google Scholar 

  20. Basu A, Teicher BA, Lazo JS. Involvement of protein kinase C in phorbol ester-induced sensitization of HeLa cells to cis-diamminedichloroplatinum (II). J Biol Chem 1990; 265:8451–8457.

    CAS  PubMed  Google Scholar 

  21. Isonishi S, Horn DK, Eastman A, Howell SB. Enhancement of sensitivity of platinum(II)-containing drugs by activation of protein kinase C in a human ovarianc carcinoma cell line. Br J Cancer 1994; 69:217–221.

    Article  CAS  PubMed  Google Scholar 

  22. Mann SC, Andrews PA, Howell SB. Modulation of cis-diamminedichloroplatinum(II) accumulation and sensitivity by forskolin and 3-isobutyl-1-methylxanthine in sensitive and resistant human ovarian carcinoma cells. Int J Cancer 1991; 48:866–872.

    Article  CAS  PubMed  Google Scholar 

  23. Hartwel Leland H, Kastan Michael B. Cell Cycle Control and Cancer. Science 1994; 266:1821–1828.

    Article  Google Scholar 

  24. Fritsche M, Haessler C, Brandner G. Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents. Oncogene 1993; 8:307–318.

    CAS  PubMed  Google Scholar 

  25. Xiong Y, Harmon GJ, Zhang H, Casso D, Kobayashi R, Beach D. P21 is a universal inhibitor of cyclin kinases. Nature 1994; 366:701–703.

    Article  Google Scholar 

  26. Peter M, Herskowitz I. Joining the complex: cyclin-dependent kinase inhibitory proteins and the cell cycle. Cell 1994; 79:181–184.

    Article  CAS  PubMed  Google Scholar 

  27. Nevins R. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 1992; 258:424–429.

    Article  CAS  PubMed  Google Scholar 

  28. Reed C. Bcl-2 and the regulation of programmed cell death. Mini-review: Cellular mechanisms of disease series. J Cell Biol 1994; 124:1–6.

    Article  CAS  PubMed  Google Scholar 

  29. Newmeyer DD, Farschon DM, Reed JC. Cell-free apoptosis in xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria. Cell 1994; 79:353–364.

    Article  CAS  PubMed  Google Scholar 

  30. Lazebnik YA, Cole S, Cooke CA, Nelson WG, Earnshaw WC. Nuclear events of apoptosis in vitro in cell-free mitotic extracts: a model system for analysis of the active phase of apoptosis. Journal of Cellular Biology 1993; 123:7–22.

    Article  CAS  Google Scholar 

  31. Oltvai ZN, Korsmeyer SJ. Checkpoints of dueling dimers foil death wishes. Cell 1994; 79:189–192.

    Article  CAS  PubMed  Google Scholar 

  32. Yang Elizabeth, Zha Jiping, Jockei Jennifer, Boise Lawrence H, Thompson Craig B, Korsmeyer Stanley J. Bad, a Heterodimeric Partner for Bcl-XL and Bcl-2, Displaces Bax and Promotes Cell Death. Cell 1995; 80:285–291.

    Article  CAS  PubMed  Google Scholar 

  33. Miyashita T, Reed JC. Tumor Suppressor p53 is a Direct Transcriptional Activator of the Human bax Gene. Cell 1995; 80:293–299.

    Article  CAS  PubMed  Google Scholar 

  34. Lowe Scott W, Ruley HEarl, Jacks Tyler, Housman David E. p53-Dependent Apoptosis Modulates the Cytotoxicity of Anticancer Agents. Cell 1993; 74:957–967.

    Article  Google Scholar 

  35. Lowe SW, Bodis S, McClatchey A, et al. p53 status and the efficacy of cancer therapy in vivo. Science 1994; 266:807–810.

    Article  CAS  PubMed  Google Scholar 

  36. Fujiwara Toshiyoshi, Grimm Elizabeth A, Mukhopadhyay Tapas, Zhang Wei-Wei, Owen-Schaub Laurie B, Roth Jack A. Induction of Chemosensitivity in Human Lung Cancer Cells in Vivo by Adenovirus-mediated Transfer of the Wild-Type p53 Gene. Cancer Res 1994; 54:2287–2291.

    CAS  PubMed  Google Scholar 

  37. Miyashita T, Krajewski S, Krajewska M, et al. Tumor suppressor p53 is a regulator of bcl-2 and bax in gene expression in vitro and in vivo. Oncogene 1994; 9:1799–1805.

    CAS  PubMed  Google Scholar 

  38. Selvakumaran, M, Lin HK, Miyashita T, et al. Immediate early up-regulation of bax expression by p53 but not TGFB1: a paradigm for distinct apoptotic pathways. Oncogene 1994; 9:1791–1798.

    CAS  PubMed  Google Scholar 

  39. Miyashita, T, Harigal M, Hanada M, Reed JC. Identification of a p53-dependent negative response element in the bcl-2 gene. Cancer Res 1994; 54:3131–3135.

    CAS  PubMed  Google Scholar 

  40. Zinszner H, Albalat R, Ron D. A novel effector domain from the RNA-binding protein TLS or EWS is required for oncogenic transformation by CHOP. Genes & Dev 1995; 8:2513–2526.

    Google Scholar 

  41. Fornace AJ, Jr., Jackman J, Hollander MC, Hoffman-Liebermann B, Liebermann DH. Genotoxic-stress-response genes and growth-arrest-genes. Annal N Y Acad Sci 1992; 139-153.

    Google Scholar 

  42. Fornace AJ, Jr., Nebert DW, Hollander C, et al. Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents. Mol Cell Biol 1989; 9:4196–4203.

    CAS  PubMed  Google Scholar 

  43. Chen, Q, Yu K, Holbrook NJ, Stevens JL. Activation of the growth arrest and DNA damage-inducible gene gadd 153 by nephrotoxic cysteine conjugates and ditiothreitol. J Biol Chem 1992; 267:8207–8212.

    CAS  PubMed  Google Scholar 

  44. Price BD, Calderwood SK. Gadd 45 and gadd 153 messenger RNA levels are increased during hypoxia and after exposure of cells to agents which elevate the levels of the glucose-regulated proteins. Cancer Res 1992; 52:3814–3817.

    CAS  PubMed  Google Scholar 

  45. Luethy JD, Holbrook NJ. The pathway regulating GADD153 induction in response to DNA damage is independent of protein kinase C of tyrosine kinases. Cancer Res 1994; 54:1902–1906.

    Google Scholar 

  46. Luethy JD, Holbrook NJ. Activation of the gadd153 promoter by genotoxic agents: a rapid and specific response to DNA damage. Cancer Res 1992; 52:5–10.

    CAS  PubMed  Google Scholar 

  47. Fornace AJ, Jr., Alamo Jr I, Hollander MC. DNA damage-inducible transcripts in mammalian cells. Proc Natl Acad Sci USA 1988; 85:8800–8804.

    Article  CAS  PubMed  Google Scholar 

  48. Park JS, Luethy JD, Wang MG, et al. Isolation, characterization and chromosomal localization of the human GADD153 gene. Gene 1992; 116:259–267.

    Article  CAS  PubMed  Google Scholar 

  49. Ron D, Habener JF. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes & Dev 1992; 6:439–453.

    Article  CAS  Google Scholar 

  50. Aman, P, Ron D, Mandahl N. Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11). Genes, Chromosomes, and Cancer 1992; 5:278–285.

    Article  CAS  PubMed  Google Scholar 

  51. Panagopoulos, I, Mandahl N, Ron D, et al. Characterization of the CHOP Breakpoints and Fusion Transcripts in Myxoid Lipsarcomas with the 12;16 Translocation. Cancer Res 1994; 54:6500–6503.

    CAS  PubMed  Google Scholar 

  52. Zhan, Q, Lord KA, Alamo I, Jr., et al. The gadd and MyD Genes Define a Novel Set of Mammalian Genes Encoding Acidic Proteins That Synergistically Suppress Cell Growth. Mol Cell Biol 1994; 2361-2371.

    Google Scholar 

  53. Ron, D, Habener JF. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes and Development 1992; 6:439–453.

    Article  CAS  PubMed  Google Scholar 

  54. Gately DP, Jones JA, Christen RD, Howell SB. Induction of the growth arrest and DNA damage inducible gene gadd153 by cisplatin in vitro and in vivo. Cancer Chemother Pharmacol 1994; submitted

    Google Scholar 

  55. Jones JA, Gately DP, Barton RA, et al. Induction of gadd153 in human melanoma xenografts as an indicator of genotoxic injury. Cell Pharmacol 1994; 1:233–237.

    CAS  Google Scholar 

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© 1996 Springer Science+Business Media New York

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Howell, S.B., Gately, D.P., Christen, R.D., Los, G. (1996). The Cisplatin-Induced Cellular Injury Response. In: Pinedo, H.M., Schornagel, J.H. (eds) Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0218-4_25

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  • DOI: https://doi.org/10.1007/978-1-4899-0218-4_25

  • Publisher Name: Springer, Boston, MA

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