Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in Apc(Min/+) mice - PubMed (original) (raw)

. 2010 Dec 1;16(23):5703-11.

doi: 10.1158/1078-0432.CCR-10-1990. Epub 2010 Oct 28.

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

Affiliations

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

Lucia Fini et al. Clin Cancer Res. 2010.

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 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.

©2010 AACR.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

Dr. Ricciardiello received a research grant by SLA Pharma AG.

Figures

Fig. 1

Fig. 1

Effect of EPA-FFA dietary supplementation on lipid peroxidation. Significant protection from lipid peroxidation was observed among EPA-FFA 5% treated groups. Data are presented as mean ± SD.

Fig. 2

Fig. 2

Effect of EPA-FFA dietary supplementation on polyp size in the intestine of ApcMin/+ mice. The EPA-FFA 5% arm displayed more polyps measuring ≤ 1 mm compared to the other groups. Data are presented as mean ± SD.

Fig. 3

Fig. 3

EPA-FFA reduces COX-2 expression. A, representative COX-2 IHC in tissues from the small intestine and colon of ApcMin/+ mice. B, quantification of COX-2 staining. A significant reduction in COX-2 expression was observed in the small intestine and colon of EPA-FFA–treated animals. Data are presented as mean ± SD.

Fig. 4

Fig. 4

EPA-FFA inhibits cellular proliferation. A, representative Ki-67 IHC in tissues from small intestines and colons of ApcMin/+ mice. B, quantification of Ki-67 staining. While a significant reduction of proliferation was observed in the small intestine and colon of animals fed EPA-FFA 5%, the effect of EPA-FFA 2.5% was restricted to the colon. Data are presented as mean ± SD.

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