title: The role of a ginseng saponin metabolite as a DNA methyltransferase inhibitor in colorectal cancer cells.
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.
authors: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea.
authors: Kyoung Ah
authors: KA
authors: Kang
authors: Hee Sun
authors: HS
authors: Kim
authors: Dong Hyun
authors: DH
authors: Kim
authors: Jin Won
authors: JW
authors: Hyun
mesh_terms: D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D036145:Ginsenosides / Q000737:chemistry / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D005894:Panax / Q000737:chemistry*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012503:Saponins / Q000008:administration & dosage* / Q000737:chemistry; D051901:Smad4 Protein / Q000096:biosynthesis
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D036145:Ginsenosides; D012503:Saponins; D051901:Smad4 Protein; C493729:Runx3 protein, human; C497796:SMAD4 protein, human; C112772:ginsenoside compound K; C000619380:DNMT1 protein, human