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


CONCLUSIONS
The study suggests that caspase activation is not synonymous with apoptosis and that activation of caspases may not necessarily induce cell death.
Yang
Shi Yu
SY
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
Bolvin
Capucine
C
Sales
Kevin M
KM
Fuller
Barry
B
Seifalian
Alexander M
AM
Winslet
Marc C
MC
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007527:Isoenzymes; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D017526:Receptor, IGF Type 1 / Q000378:metabolism
D007527:Isoenzymes; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D020169:Caspases