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

<p>Abstract</p> <p>Background</p> <p>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...

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Main Authors: Seifalian Alexander M, Fuller Barry J, Sales Kevin M, Yang Shi Yu, Winslet Marc C
Format: Article
Language:English
Published: BMC 2008-02-01
Series:Molecular Cancer
Online Access:http://www.molecular-cancer.com/content/7/1/17
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spelling doaj-4c893e8c807d432998a834565630ab8c2020-11-24T21:49:13ZengBMCMolecular Cancer1476-45982008-02-01711710.1186/1476-4598-7-17Inducing apoptosis of human colon cancer cells by an IGF-I D domain analogue peptideSeifalian Alexander MFuller Barry JSales Kevin MYang Shi YuWinslet Marc C<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p> http://www.molecular-cancer.com/content/7/1/17
collection DOAJ
language English
format Article
sources DOAJ
author Seifalian Alexander M
Fuller Barry J
Sales Kevin M
Yang Shi Yu
Winslet Marc C
spellingShingle Seifalian Alexander M
Fuller Barry J
Sales Kevin M
Yang Shi Yu
Winslet Marc C
Inducing apoptosis of human colon cancer cells by an IGF-I D domain analogue peptide
Molecular Cancer
author_facet Seifalian Alexander M
Fuller Barry J
Sales Kevin M
Yang Shi Yu
Winslet Marc C
author_sort Seifalian Alexander M
title Inducing apoptosis of human colon cancer cells by an IGF-I D domain analogue peptide
title_short Inducing apoptosis of human colon cancer cells by an IGF-I D domain analogue peptide
title_full Inducing apoptosis of human colon cancer cells by an IGF-I D domain analogue peptide
title_fullStr Inducing apoptosis of human colon cancer cells by an IGF-I D domain analogue peptide
title_full_unstemmed Inducing apoptosis of human colon cancer cells by an IGF-I D domain analogue peptide
title_sort inducing apoptosis of human colon cancer cells by an igf-i d domain analogue peptide
publisher BMC
series Molecular Cancer
issn 1476-4598
publishDate 2008-02-01
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>
url http://www.molecular-cancer.com/content/7/1/17
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