This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kobayashi, N. Articles by Aronson, W. J. Search for Related Content PubMed PubMed Citation Articles by Kobayashi, N. Articles by Aronson, W. J. Related Collections Preclinical Intervention Preclinical Intervention: In Vivo (Animals): Drugs, Nutritional Interventions, Mechanisms

Effect of Altering Dietary -6/-3 Fatty Acid Ratios on Prostate Cancer Membrane Composition, Cyclooxygenase-2, and Prostaglandin E₂

Authors' Affiliations: Departments of ¹ Urology and ² Biostatistics, Division of ³ Clinical Nutrition and ⁴ Hematology-Oncology, Department of Medicine, ⁵ Division of Pediatric Endocrinology, Department of Pediatrics, Department of Pathology, University of California, Los Angeles School of Medicine, Departments of ⁶ Physiological Sciences and ⁷ Pathology, University of California, Los Angeles; ⁸ Urology Section, Department of Surgery, Veterans Administration, Greater Los Angeles Healthcare System, Los Angeles, California; ⁹ Boston University School of Medicine, Boston, Massachusetts; ¹⁰ Department of Surgery, Veterans Administration Medical Center; ¹¹ Urology Section, Department of Surgery, Duke University School of Medicine, Durham, North Carolina; and ¹² Department of Cardiology, School of Medicine, University of California School of Medicine, Los Angeles, California

Requests for reprints: William J. Aronson, Department of Urology, University of California at Los Angeles, 66-124 Center for the Health Sciences, Box 951738, Los Angeles, CA 90095-1738. Phone: 310-268-3446; Fax: 310-268-4858; E-mail: waronson{at}ucla.edu.

Purpose: To determine whether altering the dietary content of -6 (n-6) and -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.

This article has been cited by other articles:

				M. F. McEntee, C. Ziegler, D. Reel, K. Tomer, A. Shoieb, M. Ray, X. Li, N. Neilsen, F. B. Lih, D. O'Rourke, et al. Dietary n-3 Polyunsaturated Fatty Acids Enhance Hormone Ablation Therapy in Androgen-Dependent Prostate Cancer Am. J. Pathol., July 1, 2008; 173(1): 229 - 241. [Abstract] [Full Text] [PDF]

				N. Kobayashi, R. J. Barnard, J. Said, J. Hong-Gonzalez, D. M. Corman, M. Ku, N. B. Doan, D. Gui, D. Elashoff, P. Cohen, et al. Effect of Low-Fat Diet on Development of Prostate Cancer and Akt Phosphorylation in the Hi-Myc Transgenic Mouse Model Cancer Res., April 15, 2008; 68(8): 3066 - 3073. [Abstract] [Full Text] [PDF]

				A. Angelucci, S. Garofalo, S. Speca, A. Bovadilla, G. L. Gravina, P. Muzi, C. Vicentini, and M. Bologna Arachidonic acid modulates the crosstalk between prostate carcinoma and bone stromal cells Endocr. Relat. Cancer, March 1, 2008; 15(1): 91 - 100. [Abstract] [Full Text] [PDF]