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

Koo Lee Seung, Seung Kang Jae, Jung Jung Da, Young Hur Dae, Eun Kim Jee, Eunsil Hahm, Seyeon Bae, Woo Kim Hyung, Daejin Kim, Joo Cho Byung, Daeho Cho, Hoon Shin Dong, Young Il Hwang, Jae Lee Wang

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37 Citations (Scopus)

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 1 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.

Original languageEnglish
Pages (from-to)180-188
Number of pages9
JournalJournal of Cellular Physiology
Volume216
Issue number1
DOIs
Publication statusPublished - 2008 Jul
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Seung, K. L., Jae, S. K., Da, J. J., Dae, Y. H., Jee, E. K., Hahm, E., Bae, S., Hyung, W. K., Kim, D., Byung, J. C., Cho, D., Dong, H. S., Hwang, Y. I., & Wang, J. L. (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. Journal of Cellular Physiology, 216(1), 180-188. https://doi.org/10.1002/jcp.21391