Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions

Compound K (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol, CK), an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to inhibit cell growth in a variety of cancers. However, the mechanisms are not completely understood, especially in colorectal cancer (CRC). A xe...

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Bibliographic Details
Published in:International journal of molecular sciences 2013-01, Vol.14 (2), p.2980-2995
Main Authors: Zhang, Zhiyu, Du, Guang-Jian, Wang, Chong-Zhi, Wen, Xiao-Dong, Calway, Tyler, Li, Zejuan, He, Tong-Chuan, Du, Wei, Bissonnette, Marc, Musch, Mark W, Chang, Eugene B, Yuan, Chun-Su
Format: Article
Language:English
Subjects:
Animal models
Apoptosis
Cell cycle
cell cycle arrest
Cell growth
Colon cancer
Colorectal cancer
compound K
cyclin D1
Cyclin-dependent kinase 4
Drug resistance
Electronic mail systems
G1 phase
Ginseng
ginsenoside
ginsenosides
Intestine
Kinases
Medical research
Medicine
Metabolites
p53 protein
p53/p21
Saponins
Smad3 protein
Transcription activation
Tumors
Western blotting
xenograft
Xenografts
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Summary:Compound K (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol, CK), an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to inhibit cell growth in a variety of cancers. However, the mechanisms are not completely understood, especially in colorectal cancer (CRC). A xenograft tumor model was used first to examine the anti-CRC effect of CK in vivo. Then, multiple in vitro assays were applied to investigate the anticancer effects of CK including antiproliferation, apoptosis and cell cycle distribution. In addition, a qPCR array and western blot analysis were executed to screen and validate the molecules and pathways involved. We observed that CK significantly inhibited the growth of HCT-116 tumors in an athymic nude mouse xenograft model. CK significantly inhibited the proliferation of human CRC cell lines HCT-116, SW-480, and HT-29 in a dose- and time-dependent manner. We also observed that CK induced cell apoptosis and arrested the cell cycle in the G1 phase in HCT-116 cells. The processes were related to the upregulation of p53/p21, FoxO3a-p27/p15 and Smad3, and downregulation of cdc25A, CDK4/6 and cyclin D1/3. The major regulated targets of CK were cyclin dependent inhibitors, including p21, p27, and p15. These results indicate that CK inhibits transcriptional activation of multiple tumor-promoting pathways in CRC, suggesting that CK could be an active compound in the prevention or treatment of CRC.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms14022980