Mechanistic insight into the ability of American ginseng to suppress colon cancer associated with colitis

Abstract

We have recently shown that American ginseng (AG) prevents and treats mouse colitis. Because both mice and humans with chronic colitis have a high colon cancer risk, we tested the hypothesis that AG can be used to prevent colitis-driven colon cancer. Using the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of ulcerative colitis, we show that AG can suppress colon cancer associated with colitis. To explore the molecular mechanisms of the anticancer effects of AG, we also carried out antibody array experiments on colon cells isolated at a precancerous stage. We found there were 82 protein end points that were either significantly higher (41 proteins) or significantly lower (41 proteins) in the AOM + DSS group compared with the AOM-alone (control) group. In contrast, there were only 19 protein end points that were either significantly higher (10 proteins) or significantly lower (9 proteins) in the AOM + DSS + AG group compared with the AOM-alone (control) group. Overall, these results suggest that AG keeps the colon environment in metabolic equilibrium when mice are treated with AOM + DSS and gives insight into the mechanisms by which AG protects from colon cancer associated with colitis.

Fig. 1.

Experimental protocol for the AOM/DSS mouse model of UC-driven colon cancer.

Fig. 2.

Tumor formation in colons of mice treated with AOM + DSS is prevented when these mice consume AG (75 p.p.m.) in their chow. (A) Colons stained with methylene blue. Arrows indicate macroscopic tumors. (B) Representative H&E sections. The DSS-only group shows an area of ulceration and inflammation. The AOM + DSS group shows a polypoid adenoma with high-grade dysplasia, characteristic of tumors in this group.

Fig. 3.

Confirmation of antibody array data by western blot analysis. Lysates from CD45− epithelial cells and CD45+ inflammatory cells were examined in AOM, AOM + DSS and AOM + DSS + AG groups. Results shown for the CD45− epithelial cells are consistent with antibody array data analysis for six of the proteins/posttranslational modifications.