Effects of chemoprotective diets on crypt adult stem cells u the cells of origin of colon cancer
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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 n3 polyunsaturated fatty acids (PUFAs), mainly found in fish oil, exert chemoprotective and antiinflammatory properties in part by modulating apoptotic, Wnt, and/or NFB related pathways. However, the effects of diet on colonic stem cells are unknown. Therefore, we determined whether the combination of fish oil and curcumin reduced colon cancer risk by promoting targeted apoptosis of damaged colonic stem cells at the initiation stage of cancer. Lgr5EGFPIREScreERT2 knock in mice (n=10 per treatment) were fed diets containing corn oil curcumin (COC) or fish oil curcumin (FOC) for 3 weeks. Apoptosis, cell proliferation and DNA damage in Lgr5+ stem cells were quantified 12 h post carcinogen (azoxymethane) injection. Interestingly, mice fed FO diets exhibited 15% fewer stem cells per crypt and an enhanced resistance to DNA damage, with 52% fewer damaged stem cells. For those stem cells exhibiting DNA damage, FO feeding enhanced targeted apoptosis by 24% compared to CO diets. In contrast, curcumin had no significant effects on stem cell responses. These novel results demonstrate the chemoprotective ability of external dietary cues to impact intestinal stem cell responses following carcinogen exposure.
