Inducing apoptosis of human colon cancer cells by an IGF-I D domain analogue peptide

Shi Yu Yang¹ , Kevin M Sales¹ , Barry J Fuller¹ , Alexander M Seifalian¹ and Marc C Winslet¹^,2^,3

¹University Department of Surgery, Royal Free & University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK

²Royal Free Hampstead NHS Trust Hospital, London, UK

³University College Hospital, London, UK

author email corresponding author email

Molecular Cancer 2008, 7:17doi:10.1186/1476-4598-7-17


Published:	8 February 2008

Abstract

Background

The resistance of tumour cells to apoptosis is a major contributor to the limited effectiveness of chemotherapies. Insulin-like growth factor I (IGF-I) has potential to protect cancer cells from variety of apoptotic challenges. This study was carried out to investigate the effect of a novel IGF-I receptor antagonist on apoptosis in colon cancer cells.

Results

We have designed and synthesised a novel antagonist of IGF-I receptor. The effect of this antagonist on human colon cancer cell proliferation was examined by a non-radioactive assay; the apoptosis was revealed by determining the activities of cellular caspases3/7, 8 and 9. The apoptosis pathways were investigated by examining the levels of pro-apoptosis proteins with Western blotting. Following 40 hours treatment with the novel antagonist peptide, colon cancer cell Caspase 3/7 activities increased 2–7 times; Caspase 8 activities increased 2–5 times and Caspase 9 increased 1.2–1.6 times. The proliferation of cancer cell was inhibited by 14–15%. The data showed that the antagonist induced colon cancer cell apoptosis and inhibited cancer cell proliferation. The different changes of Caspase 3/7, 8 and 9 activities suggested that the extrinsic pathways may play a major role in the antagonist peptide-induced apoptosis.

Conclusion

This is the first report on this novel antagonist to induce human colon cancer cell apoptosis and inhibit cancer cell proliferation. These results suggest that IGF-I receptor antagonists may have the potential to be developed as a novel therapy for colon cancers in the future.