Seung Koo Lee and Jae Seung Kang are contributed equally to this work.
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†
Article first published online: 22 FEB 2008
Copyright © 2008 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 216, Issue 1, pages 180–188, July 2008
How to Cite
Lee, S. K., Kang, J. S., Jung, D. J., Hur, D. Y., Kim, J. E., Hahm, E., Bae, S., Kim, H. W., Kim, D., Cho, B. J., Cho, D., Shin, D. H., Hwang, Y.-I. and Lee, W. J. (2008), 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. J. Cell. Physiol., 216: 180–188. doi: 10.1002/jcp.21391
- Issue published online: 22 APR 2008
- Article first published online: 22 FEB 2008
- Manuscript Accepted: 10 DEC 2007
- Manuscript Received: 31 OCT 2007
- Korea Science & Engineering Foundation (KOSEF)
- Tumor Immunity Medical Research Center (TIMRC). Grant Number: R13-2002-025-02001-0
- Research Center for Women's Disease (RCWD; SRC program). Grant Number: R11-2005-017-02003-0
- Sookmyung Women's University
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. J. Cell. Physiol. 216: 180–188, 2008. © 2008 Wiley-Liss, Inc.