Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in ApcMin/+ mice

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

54 Citations (Scopus)

Abstract

Purpose: 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 ApcMin/+ mice. Experimental design: ApcMin/+ 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 ApcMin/+ 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 1mmin size were predominantly found in the EPA-FFA5% arm whereas those 1 to 3mmin 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.

Original languageEnglish
Pages (from-to)5703-5711
Number of pages9
JournalClinical Cancer Research
Volume16
Issue number23
DOIs
Publication statusPublished - Dec 2010
Externally publishedYes

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    Fini, L., Piazzi, G., Ceccarelli, C., Daoud, Y., Belluzzi, A., Munarini, A., Graziani, G., Fogliano, V., Selgrad, M., Garcia, M., Gasbarrini, A., Genta, R. M., Boland, C. R., & Ricciardiello, L. (2010). Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in ApcMin/+ mice. Clinical Cancer Research, 16(23), 5703-5711. https://doi.org/10.1158/1078-0432.CCR-10-1990