Compound K, a ginsenoside metabolite, inhibits colon cancer growth via multiple pathways including p53-p21 interactions

Zhiyu Zhang, Guang Jian Du, Chong Zhi Wang, Xiao Dong Wen, Tyler Calway, Zejuan Li, Tong Chuan He, Wei Du, Marc Bissonnette, Mark W. Musch, Eugene B. Chang, Chun Su Yuan

Research output: Contribution to journalArticle

56 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2980-2995
Number of pages16
JournalInternational journal of molecular sciences
Volume14
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Cell cycle arrest
  • Colorectal cancer
  • Compound K
  • Ginsenoside
  • P53/p21
  • Xenograft

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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