The role of a ginseng saponin metabolite as a DNA methyltransferase inhibitor in colorectal cancer cells

  • Authors:
    • Kyoung Ah Kang
    • Hee Sun Kim
    • Dong Hyun Kim
    • Jin Won Hyun
  • View Affiliations

  • Published online on: May 2, 2013     https://doi.org/10.3892/ijo.2013.1931
  • Pages: 228-236
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Abstract

Hypermethylation of runt-related transcription factor 3 (RUNX3) promoter regions occurs in at least 65% of colorectal cancer cell lines. Compound K, the main metabolite of ginseng saponin, induced demethylation of a RUNX3 promoter in HT-29 human colorectal cancer cells, assessed by methylation-specific PCR and the quantitative pyrosequencing analysis. The demethylation of RUNX3 in compound K-treated cells resulted in the re-expression of RUNX3 mRNA, protein and the localization into the nucleus. Demethylation of the RUNX3 gene by compound K occurred via inhibition of the expression and activity of DNA methyltransferase 1 (DNMT1). Compound K also significantly induced RUNX3-mediated expression of Smad4 and Bim. DNMT1 inhibitory activity by compound K was related to extracellular signal-regulated kinase (ERK) inhibition, assessed by siRNA transfection on DNMT1 and ERK. In conclusion, compound K significantly inhibits the growth of colorectal cancer cells by inhibiting DNMT1 and reactivating epigenetically-silenced genes. Ginseng saponin is a potential candidate as DNMT1 inhibitor in the chemoprevention of cancer.
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July 2013
Volume 43 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kang KA, Kim HS, Kim DH and Hyun JW: The role of a ginseng saponin metabolite as a DNA methyltransferase inhibitor in colorectal cancer cells. Int J Oncol 43: 228-236, 2013
APA
Kang, K.A., Kim, H.S., Kim, D.H., & Hyun, J.W. (2013). The role of a ginseng saponin metabolite as a DNA methyltransferase inhibitor in colorectal cancer cells. International Journal of Oncology, 43, 228-236. https://doi.org/10.3892/ijo.2013.1931
MLA
Kang, K. A., Kim, H. S., Kim, D. H., Hyun, J. W."The role of a ginseng saponin metabolite as a DNA methyltransferase inhibitor in colorectal cancer cells". International Journal of Oncology 43.1 (2013): 228-236.
Chicago
Kang, K. A., Kim, H. S., Kim, D. H., Hyun, J. W."The role of a ginseng saponin metabolite as a DNA methyltransferase inhibitor in colorectal cancer cells". International Journal of Oncology 43, no. 1 (2013): 228-236. https://doi.org/10.3892/ijo.2013.1931