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

Title
The role of a ginseng saponin metabolite as a DNA methyltransferase inhibitor in colorectal cancer cells
Authors
Kang K.A.Kim H.S.Kim D.H.Hyun J.W.
Ewha Authors
김희선
SCOPUS Author ID
김희선scopus
Issue Date
2013
Journal Title
International Journal of Oncology
ISSN
1019-6439JCR Link
Citation
vol. 43, no. 1, pp. 228 - 236
Indexed
SCI; SCIE; SCOPUS WOS scopus
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.
DOI
10.3892/ijo.2013.1931
Appears in Collections:
의과대학 > 의학과 > Journal papers
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