American ginseng suppresses Western diet-promoted tumorigenesis in model of inflammation-associated colon cancer: role of EGFR

BMC Complementary and Alternative Medicine

Research Article

Yunwei Wang¹  Karen E Kim¹  Eugene B Chang¹  Marc Bissonnette¹  Anirudh Kulkarni¹  Urszula Dougherty¹  Reba Mustafi¹  Vani J Konda¹  Mark W Musch¹  John Hart²  Glyn Dawson³  Chun-Su Yuan⁴  Chong-Zhi Wang⁴ 

[1] Department of Medicine, University of Chicago, Chicago, IL, USA;Department of Pathology, University of Chicago, Chicago, IL, USA;Department of Pediatrics, University of Chicago, 60637, Chicago, Illinois, USA;Tang Center for Herbal Medicine Research, and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, USA;

关键词: Ginsenoside;    Dextran Sulfate Sodium;    Western Diet;    Epidermal Growth Factor Receptor Signal;    American Ginseng;   

DOI  :  10.1186/1472-6882-11-111

 received in 2011-08-21, accepted in 2011-11-09,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundWestern diets increase colon cancer risk. Epidemiological evidence and experimental studies suggest that ginseng can inhibit colon cancer development. In this study we asked if ginseng could inhibit Western diet (20% fat) promoted colonic tumorigenesis and if compound K, a microbial metabolite of ginseng could suppress colon cancer xenograft growth.MethodsMice were initiated with azoxymethane (AOM) and, two weeks later fed a Western diet (WD, 20% fat) alone, or WD supplemented with 250-ppm ginseng. After 1 wk, mice received 2.5% dextran sulfate sodium (DSS) for 5 days and were sacrificed 12 wks after AOM. Tumors were harvested and cell proliferation measured by Ki67 staining and apoptosis by TUNEL assay. Levels of EGF-related signaling molecules and apoptosis regulators were determined by Western blotting. Anti-tumor effects of intraperitoneal compound K were examined using a tumor xenograft model and compound K absorption measured following oral ginseng gavage by UPLC-mass spectrometry. Effects of dietary ginseng on microbial diversity were measured by analysis of bacterial 16S rRNA.ResultsGinseng significantly inhibited colonic inflammation and tumorigenesis and concomitantly reduced proliferation and increased apoptosis. The EGFR cascade was up-regulated in colonic tumors and ginseng significantly reduced EGFR and ErbB2 activation and Cox-2 expression. Dietary ginseng altered colonic microbial diversity, and bacterial suppression with metronidazole reduced serum compound K following ginseng gavage. Furthermore, compound K significantly inhibited tumor xenograft growth.ConclusionsGinseng inhibited colonic inflammation and tumorigenesis promoted by Western diet. We speculate that the ginseng metabolite compound K contributes to the chemopreventive effects of this agent in colonic tumorigenesis.

【 授权许可】

Unknown   
© Dougherty et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.