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

International Journal of Molecular Sciences

Zhiyu Zhang³  Guang-Jian Du³  Chong-Zhi Wang³  Xiao-Dong Wen³  Tyler Calway¹  Zejuan Li²  Tong-Chuan He⁴  Wei Du⁶  Marc Bissonnette⁵  Mark W. Musch⁵  Eugene B. Chang⁵ 

[1] Department of Anesthesia & Critical Care, Pritzker School of Medicine, University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637, USA; E-Mail:;Section of Hematology/Oncology, Pritzker School of Medicine, University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637, USA; E-Mail:;Tang Center for Herbal Medicine Research, Pritzker School of Medicine, University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637, USA; E-Mails:;Department of Orthopaedic Surgery, Pritzker School of Medicine, University of Chicago, 5841 S. Maryland Ave., MC 3079, Chicago, IL 60637, USA; E-Mail:;Department of Medicine, University of Chicago, 900 E. 57th street, MB 9, Chicago, IL 60637, USA; E-Mails:;Ben May Department for Cancer Research, Pritzker School of Medicine, University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637, USA; E-Mail:

关键词: colorectal cancer;    ginsenoside;    compound K;    xenograft;    cell cycle arrest;    p53/p21;   

DOI  :  10.3390/ijms14022980

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.