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Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis‐associated colorectal cancer acting on Notch signaling and gut microbiota
Author(s) -
Piazzi Giulia,
D'Argenio Giuseppe,
Prossomariti Anna,
Lembo Vincenzo,
Mazzone Giovanna,
Candela Marco,
Biagi Elena,
Brigidi Patrizia,
Vitaglione Paola,
Fogliano Vincenzo,
D'Angelo Leonarda,
Fazio Chiara,
Munarini Alessandra,
Belluzzi Andrea,
Ceccarelli Claudio,
Chieco Pasquale,
Balbi Tiziana,
Loadman Paul M.,
Hull Mark A.,
Romano Marco,
Bazzoli Franco,
Ricciardiello Luigi
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28853
Subject(s) - eicosapentaenoic acid , polyunsaturated fatty acid , colorectal cancer , medicine , cancer research , gut flora , colitis , gastroenterology , cancer , fatty acid , endocrinology , immunology , biology , biochemistry
Inflammatory bowel diseases are associated with increased risk of developing colitis‐associated colorectal cancer (CAC). Epidemiological data show that the consumption of ω‐3 polyunsaturated fatty acids (ω‐3 PUFAs) decreases the risk of sporadic colorectal cancer (CRC). Importantly, recent data have shown that eicosapentaenoic acid‐free fatty acid (EPA‐FFA) reduces polyp formation and growth in models of familial adenomatous polyposis. However, the effects of dietary EPA‐FFA are unknown in CAC. We tested the effectiveness of substituting EPA‐FFA, for other dietary fats, in preventing inflammation and cancer in the AOM‐DSS model of CAC. The AOM‐DSS protocols were designed to evaluate the effect of EPA‐FFA on both initiation and promotion of carcinogenesis. We found that EPA‐FFA diet strongly decreased tumor multiplicity, incidence and maximum tumor size in the promotion and initiation arms. Moreover EPA–FFA, in particular in the initiation arm, led to reduced cell proliferation and nuclear β‐catenin expression, whilst it increased apoptosis. In both arms, EPA‐FFA treatment led to increased membrane switch from ω‐6 to ω‐3 PUFAs and a concomitant reduction in PGE 2 production. We observed no significant changes in intestinal inflammation between EPA‐FFA treated arms and AOM‐DSS controls. Importantly, we found that EPA‐FFA treatment restored the loss of Notch signaling found in the AOM‐DSS control and resulted in the enrichment of Lactobacillus species in the gut microbiota. Taken together, our data suggest that EPA‐FFA is an excellent candidate for CRC chemoprevention in CAC.