IGF-I activates caspases 3/7, 8 and 9 but does not induce cell death in colorectal cancer cells

BMC Cancer. 2009 May 21:9:158. doi: 10.1186/1471-2407-9-158.

Abstract

Background: Colorectal cancer is the third most common cancer in the western world. Chemotherapy is often ineffective to treat the advanced colorectal cancers due to the chemo-resistance. A major contributor to chemo-resistance is tumour-derived inhibition or avoidance of apoptosis. Insulin-like growth factor I (IGF-I) has been known to play a prominent role in colorectal cancer development and progression. The role of IGF-I in cancer cell apoptosis is not completely understood.

Methods: Using three colorectal cancer cell lines and one muscle cell line, associations between IGF-I and activities of caspase 3/7, 8 and 9 have been examined; the role of insulin-like growth factor I receptor (IGF-IR) in the caspase activation has been investigated.

Results: The results show that exogenous IGF-I significantly increases activity of caspases 3/7, 8 and 9 in all cell lines used; blocking IGF-I receptor reduce IGF-I-induced caspase activation. Further studies demonstrate that IGF-I induced caspase activation does not result in cell death. This is the first report to show that while IGF-I activates caspases 3/7, 8 and 9 it does not cause colorectal cancer cell death.

Conclusion: The study suggests that caspase activation is not synonymous with apoptosis and that activation of caspases may not necessarily induce cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspases / metabolism*
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / pathology
  • Enzyme Activation / drug effects
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Isoenzymes
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / enzymology
  • Receptor, IGF Type 1 / metabolism

Substances

  • Isoenzymes
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Caspases