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 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.

Lucia Fini, Giulia Piazzi, Claudio Ceccarelli, Yahya Daoud, Andrea Belluzzi, Alessandra Munarini, et al. (2010). Highly Purified Eicosapentaenoic Acid as Free Fatty Acids Strongly Suppresses Polyps in ApcMin/+ Mice. CLINICAL CANCER RESEARCH, 16, 5703-5711 [10.1158/1078-0432.CCR-10-1990].

Highly Purified Eicosapentaenoic Acid as Free Fatty Acids Strongly Suppresses Polyps in ApcMin/+ Mice

PIAZZI, GIULIA;CECCARELLI, CLAUDIO;BELLUZZI, ANDREA;MUNARINI, ALESSANDRA;RICCIARDIELLO, LUIGI
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 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 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.
2010
Lucia Fini, Giulia Piazzi, Claudio Ceccarelli, Yahya Daoud, Andrea Belluzzi, Alessandra Munarini, et al. (2010). Highly Purified Eicosapentaenoic Acid as Free Fatty Acids Strongly Suppresses Polyps in ApcMin/+ Mice. CLINICAL CANCER RESEARCH, 16, 5703-5711 [10.1158/1078-0432.CCR-10-1990].
Lucia Fini; Giulia Piazzi; Claudio Ceccarelli; Yahya Daoud; Andrea Belluzzi; Alessandra Munarini; Giulia Graziani; Vincenzo Fogliano; Michael Selgrad;...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/93727
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