Compound K, a metabolite of ginseng saponin, inhibits colorectal cancer cell growth and induces apoptosis through inhibition of histone deacetylase activity

Kang,Kyoung Ah; Piao,Mei  Jing; Kim,Ki  Cheon; Zheng,Jian; Yao,Cheng  Wen; Cha,Ji   Won; Kim,Hye  Sun; Kim,Dong  Hyun; Bae,Suk  Chul; Hyun,Jin  Won

doi:10.3892/ijo.2013.2129

Compound K, a metabolite of ginseng saponin, inhibits colorectal cancer cell growth and induces apoptosis through inhibition of histone deacetylase activity

Authors:
- Kyoung Ah Kang
- Mei Jing Piao
- Ki Cheon Kim
- Jian Zheng
- Cheng Wen Yao
- Ji Won Cha
- Hye Sun Kim
- Dong Hyun Kim
- Suk Chul Bae
- Jin Won Hyun
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Affiliations: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690-756, Republic of Korea, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea, Department of Microbial Chemistry, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea, Department of Biochemistry, School of Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea
Published online on: October 4, 2013 https://doi.org/10.3892/ijo.2013.2129
Pages: 1907-1914

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Abstract

In this study, we investigated the molecular mechanisms underlying the anti-proliferative effects of Compound K, with specific reference to histone modification. Exposure of HT-29 human colon cancer cells to Compound K resulted in time-dependent inhibition of histone deacetylase (HDAC) activity, mRNA and protein expression. Compound K treatment induced unmethylation of the RUNX3 promoter region such as TSA treatment and an accumulation of acetylated histones H3 and H4 within the total cellular chromatin, resulting in an enhanced ability of these histones to bind to the promoter sequences of the tumor suppressor gene Runt-related transcription factor 3 (RUNX3). Treatment of cells with Compound K increased the mRNA and protein expression of RUNX3, as well as p21, a downstream target of RUNX3. These alterations were consistent with cell cycle arrest at the G0/G1 phases and induction of apoptosis. Our results provide new insights into the mechanisms of Compound K action in human colorectal cancer cells and suggest that HDAC inhibition presents a novel approach to prevent or treat colorectal cancer.

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