The molecular mechanisms of vitamin C on cell cycle regulation in B16F10 murine melanoma

Eunsil Hahm, Dong Hoon Jin, Seung Kang Jae, Young In Kim, Seung Woo Hong, Koo Lee Seung, Na Kim Ha, Jung Jung Da, Eun Kim Jee, Hoon Shin Dong, Il Hwang Young, Seok Kim Yeong, Young Hur Dae, Yoolhee Yang, Daeho Cho, Myeong Sok Lee, Jae Lee Wang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Vitamin C has inconsistent effects on malignant tumor cells, which vary from growth stimulation to apoptosis induction. It is well known that melanoma cells are more susceptible to vitamin C than any other tumor cells, but the precise mechanism remains to be elucidated. In the present study, the proliferation of B16F10 melanoma cells was suppressed by vitamin C, which induced growth arrest in a dose-dependent manner without cytotoxic effects. Therefore, we investigated the changes in cell cycle distribution of B16F10 melanoma cells by staining DNAs with propidium iodide (PI). The growth inhibition of B16F10 melanoma by vitamin C was associated with an arrest of cell cycle distribution at G1 stage. In addition, the levels of p53-p21 Waf1/Cip1 increased during G1 arrest, which were essential for vitamin C-induced cell cycle arrest. The increased p21Waf1/Cip1 inhibited CDK2. Moreover, the activity of p53-p21Waf1/Cip1 pathway was closely related with the activation of checkpoint kinase 2 (Chk2). Inhibitor of the PI3K-family, LY294002 and the ATM/ATR inhibitor, caffeine, blocked vitamin C-induced growth arrest in B16F10 melanoma cells. These results suggest that vitamin C might be a potent agent to inhibit proliferative activity of melanoma cells via the regulation of Chk2-p53-p21Waf1/Cip1 pathway.

Original languageEnglish
Pages (from-to)1002-1010
Number of pages9
JournalJournal of cellular biochemistry
Volume102
Issue number4
DOIs
Publication statusPublished - 2007 Nov 1

Keywords

  • CDK2
  • Chk2
  • G1 arrest
  • Melanoma
  • Vitamin C
  • p21
  • p53

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Hahm, E., Jin, D. H., Jae, S. K., Kim, Y. I., Hong, S. W., Seung, K. L., Ha, N. K., Da, J. J., Jee, E. K., Dong, H. S., Young, I. H., Yeong, S. K., Dae, Y. H., Yang, Y., Cho, D., Lee, M. S., & Wang, J. L. (2007). The molecular mechanisms of vitamin C on cell cycle regulation in B16F10 murine melanoma. Journal of cellular biochemistry, 102(4), 1002-1010. https://doi.org/10.1002/jcb.21336