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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MDPI AG
2013-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/14/2/2980 |
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| author | Eugene B. Chang Mark W. Musch Marc Bissonnette Tong-Chuan He Wei Du Zejuan Li Tyler Calway Xiao-Dong Wen Zhiyu Zhang Guang-Jian Du Chong-Zhi Wang Chun-Su Yuan |
| author_facet | Eugene B. Chang Mark W. Musch Marc Bissonnette Tong-Chuan He Wei Du Zejuan Li Tyler Calway Xiao-Dong Wen Zhiyu Zhang Guang-Jian Du Chong-Zhi Wang Chun-Su Yuan |
| author_sort | Eugene B. Chang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T18:56:54Z |
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| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T18:56:54Z |
| publishDate | 2013-01-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-943b0f56736d406eb9069c19b707aa212022-12-22T03:20:17ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-01-011422980299510.3390/ijms14022980Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 InteractionsEugene B. ChangMark W. MuschMarc BissonnetteTong-Chuan HeWei DuZejuan LiTyler CalwayXiao-Dong WenZhiyu ZhangGuang-Jian DuChong-Zhi WangChun-Su YuanCompound 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.http://www.mdpi.com/1422-0067/14/2/2980colorectal cancerginsenosidecompound Kxenograftcell cycle arrestp53/p21 |
| spellingShingle | Eugene B. Chang Mark W. Musch Marc Bissonnette Tong-Chuan He Wei Du Zejuan Li Tyler Calway Xiao-Dong Wen Zhiyu Zhang Guang-Jian Du Chong-Zhi Wang Chun-Su Yuan Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions International Journal of Molecular Sciences colorectal cancer ginsenoside compound K xenograft cell cycle arrest p53/p21 |
| title | Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions |
| title_full | Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions |
| title_fullStr | Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions |
| title_full_unstemmed | Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions |
| title_short | Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions |
| title_sort | compound k a ginsenoside metabolite inhibits colon cancer growth via multiple pathways including p53 p21 interactions |
| topic | colorectal cancer ginsenoside compound K xenograft cell cycle arrest p53/p21 |
| url | http://www.mdpi.com/1422-0067/14/2/2980 |
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