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Effects of chemoprotective diets on crypt adult stem cells û the cells of origin of colon cancer (819.1)
Author(s) -
Kim Eunjoo,
Davidson Laurie A.,
Patil Bhimanagouda S.,
Jayaprakasha Guddadarangavvanahally K.,
Callaway Evelyn S.,
Turner Nancy D.,
Chapkin Robert S.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.819.1
Subject(s) - chemoprotective , azoxymethane , stem cell , curcumin , cancer stem cell , lgr5 , wnt signaling pathway , aberrant crypt foci , biology , cancer research , apoptosis , cancer , colorectal cancer , chemistry , microbiology and biotechnology , pharmacology , biochemistry , signal transduction , genetics , colonic disease
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 NFκB 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. Lgr5‐EGFP‐IRES‐creERT2 knock in mice (n=10 per treatment) were fed diets containing corn oil ± curcumin (CO±C) or fish oil ± curcumin (FO±C) 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.