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

Kyoung Ah Kang, Hee Sun Kim, Dong Hyun Kim, Jin Won Hyun

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.

Original languageEnglish
Pages (from-to)228-236
Number of pages9
JournalInternational Journal of Oncology
Volume43
Issue number1
DOIs
StatePublished - Jul 2013

Keywords

  • Colorectal cancer
  • DNA methyltransferase
  • Epigenetic alteration
  • Ginseng saponin metabolite
  • Tumor suppressor gene

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