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Int. J. Mol. Sci. 2013, 14(2), 2980-2995; doi:10.3390/ijms14022980
Article

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

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Received: 6 December 2012; in revised form: 24 January 2013 / Accepted: 25 January 2013 / Published: 31 January 2013
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Abstract: 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.
Keywords: colorectal cancer; ginsenoside; compound K; xenograft; cell cycle arrest; p53/p21 colorectal cancer; ginsenoside; compound K; xenograft; cell cycle arrest; p53/p21
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Zhang, Z.; Du, G.-J.; Wang, C.-Z.; Wen, X.-D.; Calway, T.; Li, Z.; He, T.-C.; Du, W.; Bissonnette, M.; Musch, M.W.; Chang, E.B.; Yuan, C.-S. Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions. Int. J. Mol. Sci. 2013, 14, 2980-2995.

AMA Style

Zhang Z, Du G-J, Wang C-Z, Wen X-D, Calway T, Li Z, He T-C, Du W, Bissonnette M, Musch MW, Chang EB, Yuan C-S. Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions. International Journal of Molecular Sciences. 2013; 14(2):2980-2995.

Chicago/Turabian Style

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. 2013. "Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions." Int. J. Mol. Sci. 14, no. 2: 2980-2995.



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