IGF-I protects human oral buccal mucosal epithelial cells from sodium nitroprusside-induced apoptosis via PI3-kinase

Abstract Objective Cancers of the head and neck account for the vast majority of all malignancies of the oral cavity. The insulin-like growth factor (IGF) family of proteins is well documented to have an important role in rescuing cells from apoptosis. While it is known the IGF proteins are present...

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Bibliographic Details
Published in:Growth hormone & IGF research 2008-08, Vol.18 (4), p.298-306
Main Authors: Brady, Garrett, Crean, St John, Lorenzon, Ana, Kapas, Supriya
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Apoptosis
Apoptosis - drug effects
Butadienes - pharmacology
Cancers of the head and neck
Cells, Cultured
Chromones - pharmacology
Cytoprotection - drug effects
Cytoprotection - physiology
DNA Fragmentation - drug effects
Endocrinology & Metabolism
Enzyme Inhibitors - pharmacology
Epithelial Cells - drug effects
Humans
Insulin-like growth factor
Insulin-Like Growth Factor I - pharmacology
Insulin-Like Growth Factor II - pharmacology
Keratinocytes - drug effects
Mice
Morpholines - pharmacology
Mouth Mucosa - drug effects
Nitriles - pharmacology
Nitroprusside - pharmacology
Oral keratinocytes
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Phosphatidylinositol 3-Kinases - physiology
PI3-k/Akt signaling pathway
Squamous cell carcinoma
Swiss 3T3 Cells
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Summary:Abstract Objective Cancers of the head and neck account for the vast majority of all malignancies of the oral cavity. The insulin-like growth factor (IGF) family of proteins is well documented to have an important role in rescuing cells from apoptosis. While it is known the IGF proteins are present in normal oral epithelial and cancer cells its role is not fully understood. Our aim was to study the ability of IGFs to rescue sodium nitroprusside (SNP)-induced apoptotic normal oral epithelial cells in vitro. Design Cultured normal human oral keratinocytes (NOKs) or epithelial cells were used. Apoptosis was induced by SNP then cells were exposed to IGF-I or IGF-II to rescue them. Cell viability was assessed by ELISA (for cell death and caspase 3) and FACS analysis; post receptor effects of IGF-I or IGF-II were assessed by [3 H] thymidine incorporation. Cell signaling events were measured by western blotting using antibodies against phosphorylated Akt or p42/p44 MAPK, and measuring PI3-K activity by ELISA. Results SNP induced apoptosis of NOKs and activated the PI3-K/Akt survival pathway. Exposing cells to IGF proteins prevented their apoptosis. IGF-I and -II caused significant increases in PI3-K, but not MAPK, activity. SNP and LY294002, a PI3-K inhibitor, both caused a significant rise in caspase 3 release from NOKs which was reduced in the presence of IGFs. Conclusions The data establishes the importance of IGF-activated PI3-K in rescuing cells from apoptosis. It lends further evidence to the significance of IGF proteins in the possible development of oral cancer.
ISSN:1096-6374
1532-2238
DOI:10.1016/j.ghir.2007.11.006