Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer

Citations Over TimeTop 15% of 2009 papers

Abstract

Context: Resveratrol exhibits colon cancer prevention activity in animal models; it is purported to have this activity in humans and inhibit a key signaling pathway involved in colon cancer initiation, the Wnt pathway, in vitro . Design: A phase I pilot study in patients with colon cancer was performed to evaluate the effects of a low dose of plant-derived resveratrol formulation and resveratrol-containing freeze-dried grape powder (GP) on Wnt signaling in the colon. Eight patients were enrolled and normal colonic mucosa and colon cancer tissue were evaluated by Wnt pathway-specific microarray and quantitative real-time polymerase chain reaction (qRT-PCR) pre- and post-exposure to resveratrol/GP. Results: Based on the expression of a panel of Wnt target genes, resveratrol/GP did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03) activity in inhibiting Wnt target gene expression in normal colonic mucosa. The greatest effect on Wnt target gene expression was seen following ingestion of 80 g of GP per day (p < 0.001). These results were confirmed with qRT-PCR of cyclinD1 and axinII . The inhibitory effect of GP on Wnt signal throughput was confirmed in vitro with a normal colonic mucosa-derived cell line. Conclusions: These data suggest that GP, which contains low dosages of resveratrol in combination with other bioactive components, can inhibit the Wnt pathway in vivo and that this effect is confined to the normal colonic mucosa. Further study of dietary supplementation with resveratrol-containing foods such as whole grapes or GP as a potential colon cancer preventive strategy is warranted. Trial registration: NCT00256334. Keywords: resveratrol, clinical trial, colon cancer, Wnt signaling, grapes, cancer prevention

Related Papers

• → Resveratrol and derivatives for the prevention and treatment of cancer(2010)246 cited
• → Resveratrol cytotoxicity is energy‐dependent(2019)23 cited
• Uptake of resveratrol and role of resveratrol-targeting protein, quinone reductase 2, in normally cultured human prostate cells(2009)
• → Resveratrol—The “Chateau Hormone” for Cardio Diabetic Protection(2014)1 cited
• → Resveratrol: Biochemistry and Functions(2009)2 cited