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Vitamin C suppresses proliferation of the human melanoma cell SK-MEL-2 through the inhibition of cyclooxygenase-2 (COX-2) expression and the modulation of insulin-like growth factor II (IGF-II) production
Cited 32 time in
Web of Science
Cited 38 time in Scopus
- Authors
- Issue Date
- 2008-02-26
- Publisher
- Wiley-Blackwell
- Citation
- J Cell Physiol. 216(1):180-188
- Keywords
- Animals ; Ascorbic Acid/*metabolism ; Cell Line, Tumor ; Cyclooxygenase 2/genetics/*metabolism ; Enzyme Activation ; Enzyme Inhibitors/metabolism ; Humans ; Imidazoles/metabolism ; Insulin-Like Growth Factor II/genetics/*metabolism ; Pyridines/metabolism ; RNA, Small Interfering/genetics/metabolism ; Receptor, IGF Type 1/genetics/metabolism ; Vitamins/metabolism ; p38 Mitogen-Activated Protein Kinases/genetics/metabolism ; Cell Proliferation ; Melanoma/metabolism/pathology
- Abstract
- Vitamin C plays a crucial role in the suppression of proliferation of several types of cancer. Over-expression of cyclooxygenase (COX)-2 and type I insulin-like growth factor (IGF) receptor are important for proliferation and protection from apoptosis in malignancies. However, its specific mechanisms, especially the interaction between COX-2 expression and IGF-I axis mediated by vitamin C, remain yet to be clarified. Therefore, we investigated the effects of vitamin C on the proliferation of melanoma cells via the modulation of COX-2 expression and IGF-I axis. As a result, we found that 1.0 mM vitamin C inhibits the proliferation of SK-MEL-2 without induction of apoptosis. At that moment, IGF-II production was decreased, followed by the inhibition of COX-2 activity. IGF-IR expression was also down-regulated by vitamin C treatment. It coincided with the result from the inhibition of COX-2 by NS-398 and COX-2 siRNA. In addition, the decreased IGF-IR expression by vitamin C was restored by the treatment of recombinant prostaglandin E2. Finally, we determined whether the signal pathway would be involved in vitamin C-induced IGF-II and IGF-IR down-regulation. When the cells were exposed to SB203580, a specific inhibitor of p38 MAPK, COX-2 expression was dramatically recovered. In addition, phosphorylated p38 MAPK was increased after vitamin C treatment. Taken together, vitamin C suppresses proliferation of the human melanoma cell line SK-MEL2 via the down-regulation of IGF-II production and IGF-IR expression, which is followed by the activation of p38 MAPK and the inhibition of COX-2 expression.
- ISSN
- 1097-4652 (Electronic)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18297687
https://hdl.handle.net/10371/67791
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