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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 37 time in Scopus
Authors
Lee, Seung Koo; Kang, Jae Seung; Jung, Da Jung; Hur, Dae Young; Kim, Jee Eun; Hahm, Eunsil; Bae, Seyeon; Kim, Hyung Woo; Kim, Daejin; Cho, Byung Joo; Cho, Daeho; Shin, Dong Hoon; Hwang, Young-Il; Lee, Wang Jae
Issue Date
2008-02-26
Publisher
Wiley-Blackwell
Citation
J Cell Physiol. 216(1):180-188
Keywords
AnimalsAscorbic Acid/*metabolismCell Line, Tumor*Cell ProliferationCyclooxygenase 2/genetics/*metabolismEnzyme ActivationEnzyme Inhibitors/metabolismHumansImidazoles/metabolismInsulin-Like Growth Factor II/genetics/*metabolism*Melanoma/metabolism/pathologyPyridines/metabolismRNA, Small Interfering/genetics/metabolismReceptor, IGF Type 1/genetics/metabolismVitamins/metabolismp38 Mitogen-Activated Protein Kinases/genetics/metabolism
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

http://hdl.handle.net/10371/67791
DOI
https://doi.org/10.1002/jcp.21391
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College of Medicine/School of Medicine (의과대학/대학원)Anatomy (해부학전공)Journal Papers (저널논문_해부학전공)
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