TY - JOUR
T1 - Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in ApcMin/+ mice
AU - Fini, Lucia
AU - Piazzi, Giulia
AU - Ceccarelli, Claudio
AU - Daoud, Yahya
AU - Belluzzi, Andrea
AU - Munarini, Alessandra
AU - Graziani, Giulia
AU - Fogliano, Vincenzo
AU - Selgrad, Michael
AU - Garcia, Melissa
AU - Gasbarrini, Antonio
AU - Genta, Robert M.
AU - Boland, C. Richard
AU - Ricciardiello, Luigi
PY - 2010/12/1
Y1 - 2010/12/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-10-1990
DO - 10.1158/1078-0432.CCR-10-1990
M3 - Article
C2 - 21030497
AN - SCOPUS:78650364506
SN - 1078-0432
VL - 16
SP - 5703
EP - 5711
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -