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. Richard Boland, Luigi Ricciardiello

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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 (US)
Pages (from-to)5703-5711
Number of pages9
JournalClinical Cancer Research
Volume16
Issue number23
DOIs
StatePublished - Dec 1 2010

Fingerprint

Eicosapentaenoic Acid
Polyps
Nonesterified Fatty Acids
Diet
Colorectal Neoplasms
Catenins
Cachexia
Cyclooxygenase 2 Inhibitors
Poisons
Chemoprevention
Cyclooxygenase 2
Unsaturated Fatty Acids
Arachidonic Acid
Lipid Peroxidation
Small Intestine
Intestines
Colon
Research Design
Eating
Body Weight

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fini, L., Piazzi, G., Ceccarelli, C., Daoud, Y., Belluzzi, A., Munarini, A., ... 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

Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in ApcMin/+ mice. / Fini, Lucia; Piazzi, Giulia; Ceccarelli, Claudio; Daoud, Yahya; Belluzzi, Andrea; Munarini, Alessandra; Graziani, Giulia; Fogliano, Vincenzo; Selgrad, Michael; Garcia, Melissa; Gasbarrini, Antonio; Genta, Robert M.; Boland, C. Richard; Ricciardiello, Luigi.

In: Clinical Cancer Research, Vol. 16, No. 23, 01.12.2010, p. 5703-5711.

Research output: Contribution to journalArticle

Fini, L, Piazzi, G, Ceccarelli, C, Daoud, Y, Belluzzi, A, Munarini, A, Graziani, G, Fogliano, V, Selgrad, M, Garcia, M, Gasbarrini, A, Genta, RM, Boland, CR & Ricciardiello, L 2010, 'Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in ApcMin/+ mice', Clinical Cancer Research, vol. 16, no. 23, pp. 5703-5711. https://doi.org/10.1158/1078-0432.CCR-10-1990
Fini, Lucia ; Piazzi, Giulia ; Ceccarelli, Claudio ; Daoud, Yahya ; Belluzzi, Andrea ; Munarini, Alessandra ; Graziani, Giulia ; Fogliano, Vincenzo ; Selgrad, Michael ; Garcia, Melissa ; Gasbarrini, Antonio ; Genta, Robert M. ; Boland, C. Richard ; Ricciardiello, Luigi. / Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in ApcMin/+ mice. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 23. pp. 5703-5711.
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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.",
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AU - Daoud, Yahya

AU - Belluzzi, Andrea

AU - Munarini, Alessandra

AU - Graziani, Giulia

AU - Fogliano, Vincenzo

AU - Selgrad, Michael

AU - Garcia, Melissa

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