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

Yang SY, Bolvin C, Sales KM, Fuller B, Seifalian AM, Winslet MC - BMC Cancer (2009)

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

View Article: PubMed Central - HTML - PubMed

Affiliation: University College London, Division of Surgery and Interventional Science, Royal Free & University College Medical School, Rowland Hill Street, London, UK. shiyu.yang@medsch.ucl.ac.uk

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.

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Related in: MedlinePlus

IGF-I activate caspases 3/7, 8 and 9 in HT-29 cells.  IGF-I activate caspases 3/7 (a, b, g, h), 8 (c, d, i, j) and 9 (e, f, k, l) in HT-29 cells in serum containing (SCM, a-f) and serum free (SFM, g-l) media following the treatment with different concentrations of IGF-I (1, 10, and 100 ng/ml) for 24 and 48 hours. Significance value: * P <0.05; ** P <0.01 compared to untreated cells.
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Figure 1: IGF-I activate caspases 3/7, 8 and 9 in HT-29 cells. IGF-I activate caspases 3/7 (a, b, g, h), 8 (c, d, i, j) and 9 (e, f, k, l) in HT-29 cells in serum containing (SCM, a-f) and serum free (SFM, g-l) media following the treatment with different concentrations of IGF-I (1, 10, and 100 ng/ml) for 24 and 48 hours. Significance value: * P <0.05; ** P <0.01 compared to untreated cells.

Mentions: To assess the effect of IGF-I on the activities of the main caspases (caspase 3/7, 8 and 9) in colorectal cancer cells, we treated the human HT-29 cell line with different concentrations of recombinant human IGF-I for 24 and 48 hours. The caspase activity was evaluated with cell-based homogeneous caspase-glo assay kit in serum containing medium (SCM, figure 1a–f) and serum free medium (SFM, figure 1g–l). The results shown that after treatment with IGF-I for 24 and 48 hours, HT-29 cellular caspase 3/7 activities increased in both SCM and SFM conditions in a dose dependent manner (figures 1a, b, g and 1h). It has been recognized that caspase 3/7 is activated by caspases 8 or 9, therefore these two caspases activity was also measured using the same methods under the same conditions (SCM and SFM). The results demonstrate that after treatment with IGF-I, the activity of the caspase 8 (figures 1c, d, i and 1j) and 9 (figure 1e, f, k and 1l) also increased in SCM and SFM conditions in a dose dependant manner. Caspase 8 activation is the step immediately following death-inducing signalling complex (DISC) formation. The latter is the part of the extrinsic apoptosis pathway which involves death ligands bound to cell surface death receptors. Caspase 9 activation is a part of the intrinsic apoptosis pathway, which involves cytochrome C release from the mitochondria [22]. It is interesting to note that although IGF-I increased in all three caspases (3/7, 8 and 9) activities in both SCM and SFM conditions, the level of these caspases activity in SFM conditions (figure 1g–l) is considerably higher than those in SCM conditions (figure 1a–f). This finding is consistent with a previous report which demonstrated that serum deprivation induced apoptosis [14]. Collectively these data suggested that IGF-I treatment increases human colon cancer HT-29 cell caspase 3/7, 8 and 9 activity under both SCM and SFM conditions.


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

Yang SY, Bolvin C, Sales KM, Fuller B, Seifalian AM, Winslet MC - BMC Cancer (2009)

IGF-I activate caspases 3/7, 8 and 9 in HT-29 cells.  IGF-I activate caspases 3/7 (a, b, g, h), 8 (c, d, i, j) and 9 (e, f, k, l) in HT-29 cells in serum containing (SCM, a-f) and serum free (SFM, g-l) media following the treatment with different concentrations of IGF-I (1, 10, and 100 ng/ml) for 24 and 48 hours. Significance value: * P <0.05; ** P <0.01 compared to untreated cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698923&req=5

Figure 1: IGF-I activate caspases 3/7, 8 and 9 in HT-29 cells. IGF-I activate caspases 3/7 (a, b, g, h), 8 (c, d, i, j) and 9 (e, f, k, l) in HT-29 cells in serum containing (SCM, a-f) and serum free (SFM, g-l) media following the treatment with different concentrations of IGF-I (1, 10, and 100 ng/ml) for 24 and 48 hours. Significance value: * P <0.05; ** P <0.01 compared to untreated cells.
Mentions: To assess the effect of IGF-I on the activities of the main caspases (caspase 3/7, 8 and 9) in colorectal cancer cells, we treated the human HT-29 cell line with different concentrations of recombinant human IGF-I for 24 and 48 hours. The caspase activity was evaluated with cell-based homogeneous caspase-glo assay kit in serum containing medium (SCM, figure 1a–f) and serum free medium (SFM, figure 1g–l). The results shown that after treatment with IGF-I for 24 and 48 hours, HT-29 cellular caspase 3/7 activities increased in both SCM and SFM conditions in a dose dependent manner (figures 1a, b, g and 1h). It has been recognized that caspase 3/7 is activated by caspases 8 or 9, therefore these two caspases activity was also measured using the same methods under the same conditions (SCM and SFM). The results demonstrate that after treatment with IGF-I, the activity of the caspase 8 (figures 1c, d, i and 1j) and 9 (figure 1e, f, k and 1l) also increased in SCM and SFM conditions in a dose dependant manner. Caspase 8 activation is the step immediately following death-inducing signalling complex (DISC) formation. The latter is the part of the extrinsic apoptosis pathway which involves death ligands bound to cell surface death receptors. Caspase 9 activation is a part of the intrinsic apoptosis pathway, which involves cytochrome C release from the mitochondria [22]. It is interesting to note that although IGF-I increased in all three caspases (3/7, 8 and 9) activities in both SCM and SFM conditions, the level of these caspases activity in SFM conditions (figure 1g–l) is considerably higher than those in SCM conditions (figure 1a–f). This finding is consistent with a previous report which demonstrated that serum deprivation induced apoptosis [14]. Collectively these data suggested that IGF-I treatment increases human colon cancer HT-29 cell caspase 3/7, 8 and 9 activity under both SCM and SFM conditions.

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

View Article: PubMed Central - HTML - PubMed

Affiliation: University College London, Division of Surgery and Interventional Science, Royal Free & University College Medical School, Rowland Hill Street, London, UK. shiyu.yang@medsch.ucl.ac.uk

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.

Show MeSH
Related in: MedlinePlus