Effect of Altering Dietary ω-6/ω-3 Fatty Acid Ratios on Prostate Cancer Membrane Composition, Cyclooxygenase-2, and Prostaglandin E2
- 1 August 2006
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 12 (15), 4662-4670
- https://doi.org/10.1158/1078-0432.ccr-06-0459
Abstract
Purpose: To determine whether altering the dietary content of ω-6 (n-6) and ω-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E2 (PGE2) levels. Experimental Design: Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection. Results: Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase–mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE2 levels, and decreased vascular endothelial growth factor expression. Conclusion: These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE2 and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.Keywords
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This publication has 57 references indexed in Scilit:
- Dietary Fat, Calorie Restriction, Ad Libitum Feeding, and Cancer RiskNutrition Reviews, 2009
- Cyclooxygenase-2 Expression Correlates with Local Chronic Inflammation and Tumor Neovascularization in Human Prostate CancerClinical Cancer Research, 2005
- Regression of Mouse Prostatic Intraepithelial Neoplasia by Nonsteroidal Anti-inflammatory Drugs in the Transgenic Adenocarcinoma Mouse Prostate ModelClinical Cancer Research, 2004
- Nutritional and Botanical Modulation of the Inflammatory Cascade—Eicosanoids, Cyclooxygenases, and Lipoxygenases— As an Adjunct in Cancer TherapyIntegrative Cancer Therapies, 2002
- INHIBITION OF CYCLOOXYGENASE-2 SUPPRESSES ANGIOGENESIS AND THE GROWTH OF PROSTATE CANCER IN VIVOJournal of Urology, 2000
- Association of energy and fat intake with prostate carcinoma riskCancer, 1999
- Arachidonic Acid Stimulates Prostate Cancer Cell Growth: Critical Role of 5-LipoxygenaseBiochemical and Biophysical Research Communications, 1997
- Prostaglandin synthase 2Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1996
- A Prospective Study of Dietary Fat and Risk of Prostate CancerJNCI Journal of the National Cancer Institute, 1993
- Inhibition of prostaglandin biosynthesis by eicosapentaenoic acidProstaglandins and Medicine, 1979