Anti-inflammatory Effects Of Muscadine Grape Extract In The ApcMin/+ Mouse Model Of Intestinal Tumorigenesis

Abstract

Inflammation plays a necessary role in the development and progression of colon cancer; it has been linked to cellular transformation, promotion, survival, proliferation, invasion, angiogenesis and metastasis. Muscadine grapes contain relatively high concentrations of many bioactive components that have anti-inflammatory activity. While there has been a lot of work done to uncover the anti-carcinogenic activity of the individual bioactive components of muscadine grapes (e.g. quercetin and resveratrol), there have been relatively few studies that have examined the chemopreventive effects of whole muscadine grape extracts. PURPOSE: The purpose of this study was to determine the effects of muscadine grape extract (MGE) on inflammation in a mouse model of intestinal tumorigenesis. METHODS: Female ApcMin/+ mice were randomly assigned to either placebo (P) or MGE (n=12/group) groups. Mice were given P or MGE (5%) diet from 11-18 weeks of age. This treatment regime was designed to determine the effects of MGE on inflammation in mice that already have polyp development (i.e. intervention). Tissues were collected at 18 wks of age and intestines were analyzed for polyp number and size in sections 1, 4 and 5 and for inflammatory cytokine mRNA expression and protein concentration (mucosal tissue and polyps) in section 2. RESULTS: MGE decreased mRNA expression of MCP-1, IL-1B, IL-6 and TNF-α in the mucosal tissue (P<0.05) but not in the polyp tissue. There was no effect of MGE on cytokine protein concentration in the mucosal tissue or polyps. As expected there was no effect of MGE on polyp number or size using this treatment regime; ApcMin/+ mice have already developed polyps by 11 wks of age. CONCLUSIONS: The data suggest that dietary MGE given as an intervention treatment (i.e. a time when mice already have polyps) can reduce mRNA expression of inflammatory mediators in intestinal muscosal tissue. Further research is needed to determine if this apparent reduction in inflammation translates to a better prognosis with respect to colon cancer progression.