Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Equivalent effect of DNA damage-induced apoptotic cell death or long-term cell cycle arrest on colon carcinoma cell proliferation and tumour growth

Oncogene volume 25, pages 165–175 (2006)Cite this article

Abstract

Knowledge of the type of biological reaction to chemotherapy is a prerequisite for its rational enhancement. We previously showed that irinotecan-induced DNA damage triggers in the HCT116p53wt colon carcinoma cell line a long-term cell cycle arrest and in HCT116p53−/− cells apoptosis (Magrini et al., 2002). To compare the contribution of long-term cell cycle arrest and that of apoptosis to inhibition of cell proliferation after irinotecan-induced DNA damage, we used this isogenic system as well as the cell lines LS174T (p53wt) and HT-29 (p53mut). Both p53wt cell lines responded to damage by undergoing a long-term tetraploid G1 arrest, whereas the p53mut cell lines underwent apoptosis. Cell cycle arrest as well as apoptosis caused a similar delay in cell proliferation. Irinotecan treatment also induced in mouse tumours derived from the p53wt cell lines a tetraploid G1 arrest and in those derived from the p53-deficient cell lines a transient G2/M arrest and apoptosis. The delay of tumour growth was in the same range in both groups, that is, arrest- and apoptosis-mediated tumour growth inhibition was comparable. In conclusion, cell cycle arrest as well as apoptosis may be equipotent mechanisms mediating the chemotherapeutic effects of irinotecan.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

Abbreviations

p53wt:

p53 wild type

p53mut:

p53 mutated

CPT-11:

irinotecan

SN-38:

irinotecan metabolite 7-ethyl-10-hydroxycamptothecin

ASPP:

apoptosis stimulating protein of p53

References

  • Abal M, Bras-Goncalves R, Judde JG, Fsihi H, De Cremoux P, Louvard D et al. (2004). Oncogene 23: 1737–1744.

  • Andreassen PR, Lacroix FB, Lohez OD, Margolis RL . (2001a). Cancer Res 61: 7660–7668.

  • Andreassen PR, Lohez OD, Lacroix FB, Margolis RL . (2001b). Mol Biol Cell 12: 1315–1328.

  • Bartussek C, Naumann U, Weller M . (1999). Exp Cell Res 253: 432–439.

  • Bhonde MR, Hanski ML, Magrini R, Moorthy D, Muller A, Sausville EA et al. (2005). Oncogene 24: 148–156.

  • Boyer J, McLean EG, Aroori S, Wilson P, McCulla A, Carey PD et al. (2004). Clin Cancer Res 10: 2158–2167.

  • Brown JM, Attardi LD . (2005). Nat Rev Cancer 5: 231–237.

  • Brown JM, Wouters BG . (1999). Cancer Res 59: 1391–1399.

  • Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP et al. (1998). Science 282: 1497–1501.

  • Bunz F, Hwang PM, Torrance C, Waldman T, Zhang Y, Dillehay L et al. (1999). J Clin Invest 104: 263–269.

  • Chang BD, Swift ME, Shen M, Fang J, Broude EV, Roninson IB . (2002). Proc Natl Acad Sci USA 99: 389–394.

  • Chang BD, Xuan Y, Broude EV, Zhu H, Schott B, Fang J et al. (1999). Oncogene 18: 4808–4818.

  • Clifford B, Beljin M, Stark GR, Taylor WR . (2003). Cancer Res 63: 4074–4081.

  • Crawford DF, Piwnica-Worms H . (2001). J Biol Chem 276: 37166–37177.

  • Cusack Jr JC, Liu R, Houston M, Abendroth K, Elliott PJ, Adams J et al. (2001). Cancer Res 61: 3535–3540.

  • Ducreux M, Kohne CH, Schwartz GK, Vanhoefer U . (2003). Ann Oncol 14(Suppl. 2): ii17–ii23.

  • Goldwasser F, Shimizu T, Jackman J, Hoki Y, O'Connor PM, Kohn KW et al. (1996). Cancer Res 56: 4430–4437.

  • Gunasekar P, Li L, Prabhakaran K, Eybl V, Borowitz JL, Isom GE . (2001). Toxicol Sci 64: 83–89.

  • Han Z, Wei W, Dunaway S, Darnowski JW, Calabresi P, Sedivy J et al. (2002). J Biol Chem 277: 17154–17160.

  • Hemmati PG, Gillissen B, von Haefen C, Wendt J, Starck L, Guner D et al. (2002). Oncogene 21: 3149–3161.

  • Hirose Y, Berger MS, Pieper RO . (2001). Cancer Res 61: 1957–1963.

  • Jacob S, Aguado M, Fallik D, Praz F . (2001). Cancer Res 61: 6555–6562.

  • Jansen WJ, Zwart B, Hulscher ST, Giaccone G, Pinedo HM, Boven E . (1997). Int J Cancer 70: 335–340.

  • Koike M, Fujita F, Komori K, Katoh F, Sugimoto T, Sakamoto Y et al. (2004). Cancer Sci 95: 541–546.

  • Koizumi F, Kanzawa F, Ueda Y, Koh Y, Tsukiyama S, Taguchi F et al. (2004). Int J Cancer 108: 464–472.

  • Liu MC, Gelmann EP . (2002). Semin Oncol 29: 246–257.

  • Liu R, Page C, Beidler DR, Wicha MS, Nunez G . (1999). Am J Pathol 155: 1861–1867.

  • Magrini R, Bhonde MR, Hanski ML, Notter M, Scherubl H, Boland CR et al. (2002). Int J Cancer 101: 23–31.

  • Mathijssen RH, van Alphen RJ, Verweij J, Loos WJ, Nooter K, Stoter G et al. (2001). Clin Cancer Res 7: 2182–2194.

  • Merritt AJ, Allen TD, Potten CS, Hickman JA . (1997). Oncogene 14: 2759–2766.

  • Miknyoczki SJ, Jones-Bolin S, Pritchard S, Hunter K, Zhao H, Wan W et al. (2003). Mol Cancer Ther 2: 371–382.

  • Monks A, Harris ED, Vaigro-Wolff A, Hose CD, Connelly JW, Sausville EA . (2000). Invest New Drugs 18: 95–107.

  • Motwani M, Jung C, Sirotnak FM, She Y, Shah MA, Gonen M et al. (2001). Clin Cancer Res 7: 4209–4219.

  • Nabha SM, Mohammad RM, Dandashi MH, Coupaye-Gerard B, Aboukameel A, Pettit GR et al. (2002). Clin Cancer Res 8: 2735–2741.

  • Paradis V, Youssef N, Dargere D, Ba N, Bonvoust F, Deschatrette J et al. (2001). Hum Pathol 32: 327–332.

  • Pavillard V, Agostini C, Richard S, Charasson V, Montaudon D, Robert J . (2002). Cancer Chemother Pharmacol 49: 329–335.

  • Prewett MC, Hooper AT, Bassi R, Ellis LM, Waksal HW, Hicklin DJ . (2002). Clin Cancer Res 8: 994–1003.

  • Roninson IB . (2003). Cancer Res 63: 2705–2715.

  • Samuels-Lev Y, O'Connor DJ, Bergamaschi D, Trigiante G, Hsieh JK, Zhong S et al. (2001). Mol Cell 8: 781–794.

  • Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM et al. (2002). Cell 109: 335–346.

  • Schmitt CA, Lowe SW . (2001). Drug Resist Update 4: 132–134.

  • Seoane J, Le HV, Massague J . (2002). Nature 419: 729–734.

  • Stewart ZA, Westfall MD, Pietenpol JA . (2003). Trends Pharmacol Sci 24: 139–145.

  • te Poele RH, Joel SP . (1999). Br J Cancer 81: 1285–1293.

  • te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP . (2002). Cancer Res 62: 1876–1883.

  • Uetake Y, Sluder G . (2004). J Cell Biol 165: 609–615.

  • Vanhoefer U, Harstrick A, Achterrath W, Cao S, Seeber S, Rustum YM . (2001). J Clin Oncol 19: 1501–1518.

  • Waldman T, Zhang Y, Dillehay L, Yu J, Kinzler K, Vogelstein B et al. (1997). Nat Med 3: 1034–1036.

  • Wang Y, Zhu S, Cloughesy TF, Liau LM, Mischel PS . (2004). Oncogene 23: 1283–1290.

  • Waxman DJ, Schwartz PS . (2003). Cancer Res 63: 8563–8572.

  • Whitacre CM, Zborowska E, Willson JK, Berger NA . (1999). Clin Cancer Res 5: 665–672.

  • Yu J, Wang Z, Kinzler KW, Vogelstein B, Zhang L . (2003). Proc Natl Acad Sci USA 100: 1931–1936.

Download references

Acknowledgements

We acknowledge the perfect technical assistance provided by Britta Jebautzke and the contribution of Brita Vorwerk to Figure 6. This work was supported by the Sonnenfeld Stiftung and Monika Kutzner Stiftung. SN-38 was a kind gift from Agnes Gonthier, Aventis Pharma S.A., Vitry-sur-Seine, Cedex France.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

    M R Bhonde, M-L Hanski, M Zeitz & C Hanski

  2. Department of Hematology, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

    M Notter

  3. Department of Clinical and Molecular Oncology, Charité, Campus Berlin-Buch, Berlin, Germany

    B F Gillissen & P T Daniel

Authors
  1. M R Bhonde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M-L Hanski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Notter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B F Gillissen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P T Daniel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Zeitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Hanski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Hanski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bhonde, M., Hanski, ML., Notter, M. et al. Equivalent effect of DNA damage-induced apoptotic cell death or long-term cell cycle arrest on colon carcinoma cell proliferation and tumour growth. Oncogene 25, 165–175 (2006). https://doi.org/10.1038/sj.onc.1209017

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209017

Keywords

This article is cited by

Search

Advanced search

Quick links