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

Oncogene. 2006 Jan 12;25(2):165-75. doi: 10.1038/sj.onc.1209017.


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 HCT116p53(wt) 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 (p53(wt)) and HT-29 (p53(mut)). Both p53(wt) cell lines responded to damage by undergoing a long-term tetraploid G1 arrest, whereas the p53(mut) 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 p53(wt) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis*
  • Blotting, Western
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Cell Cycle*
  • Cell Proliferation
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • DNA Damage*
  • Female
  • Flow Cytometry
  • Humans
  • Irinotecan
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mutation / genetics
  • Necrosis
  • Ploidies
  • Topoisomerase I Inhibitors
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology
  • Tumor Suppressor Protein p53 / metabolism*


  • Antineoplastic Agents, Phytogenic
  • Topoisomerase I Inhibitors
  • Tumor Suppressor Protein p53
  • Irinotecan
  • Camptothecin