Document Detail


Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in Apc(Min/+) mice.
MedLine Citation:
PMID:  21030497     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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 Richard Boland; Luigi Ricciardiello
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-10-28
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  16     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-08     Completed Date:  2011-03-31     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5703-11     Citation Subset:  IM    
Copyright Information:
©2010 AACR.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinoma / genetics,  prevention & control
Colonic Polyps / diet therapy,  genetics,  pathology,  prevention & control*
Colorectal Neoplasms / genetics,  prevention & control
Eicosapentaenoic Acid / chemistry,  isolation & purification,  pharmacology*,  therapeutic use*
Fatty Acids, Nonesterified / chemistry,  pharmacology,  therapeutic use
Genes, APC* / physiology
Genetic Predisposition to Disease
Genotype
Lipid Peroxidation / drug effects
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Tumor Burden / drug effects
Grant Support
ID/Acronym/Agency:
R01 CA072851/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; AAN7QOV9EA/Eicosapentaenoic Acid
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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