Research article

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

Shi Yu Yang¹ , Capucine Bolvin¹ , Kevin M Sales¹ , Barry Fuller¹ , Alexander M Seifalian¹ and Marc C Winslet^1,2,3

¹  University College London, Division of Surgery and Interventional Science, Royal Free & University College Medical School, Rowland Hill Street, London, NW3 2PF, UK

²  Royal Free Hampstead NHS Trust Hospital, London, UK

³  University College NHS Hospital, London, UK

author email corresponding author email

BMC Cancer 2009, 9:158doi:10.1186/1471-2407-9-158

Published:	21 May 2009

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.