Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in Apc(Min/+) mice.

Antonio Gasbarrini, Lucia Fini, Giulia Piazzi, Claudio Ceccarelli, Yahya Daoud, Andrea Belluzzi, Alessandra Munarini, Giulia Graziani, Vincenzo Fogliano, Michael Selgrad, Melissa Garcia, Robert M Genta, Richard C Boland, Luigi Ricciardiello

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Although cyclooxygenase (COX)-2 inhibitors could represent the most effective chemopreventive tool against colorectal cancer (CRC), their use in clinical practice is hampered by cardiovascular side effects. Consumption of ω-3-polyunsaturated fatty acids (ω-3-PUFAs) is associated with a reduced risk of CRC. Therefore, in this study, we assessed the efficacy of a novel 99% pure preparation of ω-3-PUFA eicosapentaenoic acid as free fatty acids (EPA-FFA) on polyps in Apc(Min/+) mice. Experimental design: Apc(Min/+) and corresponding wild-type mice were fed control diet (Ctrl) or diets containing either EPA-FFA 2.5% or 5%, for 12 weeks while monitoring food intake and body weight. RESULTS: We found that both EPA-FFA diets protected from the cachexia observed among Apc(Min/+) animals fed Ctrl diet (P < 0.0054), without toxic effect, in conjunction with a significant decrease in lipid peroxidation in the treated arms. Moreover, both EPA-FFA diets dramatically suppressed polyp number (by 71.5% and 78.6%, respectively; P < 0.0001) and load (by 82.5% and 93.4%, respectively; P < 0.0001) in both small intestine and colon. In addition, polyps less than 1 mm in size were predominantly found in the EPA-FFA 5% arm whereas those 1 to 3 mm in size were more frequent in the Ctrl arm (P < 0.0001). Interestingly, in the EPA-FFA groups, mucosal arachidonic acid was replaced by EPA (P < 0.0001), leading to a significant reduction in COX-2 expression and β-catenin nuclear translocation. Moreover, in the EPA-FFA arms, we found a significant decrease in proliferation throughout the intestine together with an increase in apoptosis. CONCLUSIONS: Our data make 99% pure EPA-FFA an excellent candidate for CRC chemoprevention.
Lingua originaleEnglish
pagine (da-a)5703-5711
Numero di pagine9
RivistaClinical Cancer Research
Volume2010
Stato di pubblicazionePubblicato - 2010

Keywords

  • eicosapentaenoic acid

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