Abstract

The majority of colon tumors are triggered by aberrant Wnt signaling in intestinal stem cells, which is an extremely efficient route towards initiating intestinal cancer. Curcumin, a component of turmeric, and n‐3 polyunsaturated fatty acids (PUFAs), mainly found in fish oil, exert chemoprotective and anti‐inflammatory properties in part by modulating apoptotic, Wnt, and/or NFkappaB related pathways. However, the chemoprotective effects of diet on colonic adult stem cells‐the cells of origin of colon cancer are unknown. Therefore, we determined whether the combination of fish oil (FO) and curcumin (C) reduce colon cancer risk by modulating targeted apoptosis, DNA damage repair and proliferation in colonic Lgr5+ stem cells at the initiation stage of cancer compared to corn oil (CO, control) by utilizing Lgr5‐EGFP‐IRES‐creERT2 knock‐in mice fed diets containing CO±C or FO±C for 3 weeks followed by carcinogen (azoxymethane) injection. Interestingly, FO+C combination synergistically increased apoptosis (TUNEL) by 5‐fold, and promoted targeted DNA repair (MGMT+) by 9‐fold in DNA damaged (gamma H2AX+) stem cells compared to control. In general, stem cells were more responsive to environmental (carcinogen & diet) cues compared to non‐stem cells. These novel results demonstrate the unique ability of colonic stem cells to respond to external cues.

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