Effect of altering dietary ω-6/ω-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E 2

Naoko Kobayashi, R. James Barnard, Susanne M. Henning, David Elashoff, Srinivasa T. Reddy, Pinchas Cohen, Pak Leung, Jenny Hong-Gonzalez, Stephen J. Freedland, Jonathan Said, Dorina Gui, Navindra P. Seeram, Laura M. Popoviciu, Dilprit Bagga, David Heber, John A. Glaspy, William J. Aronson

Research output: Contribution to journalArticle

128 Scopus citations

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 PGE 2 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 PGE 2 and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.

Original languageEnglish (US)
Pages (from-to)4662-4670
Number of pages9
JournalClinical Cancer Research
Volume12
Issue number15
DOIs
StatePublished - Aug 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kobayashi, N., Barnard, R. J., Henning, S. M., Elashoff, D., Reddy, S. T., Cohen, P., Leung, P., Hong-Gonzalez, J., Freedland, S. J., Said, J., Gui, D., Seeram, N. P., Popoviciu, L. M., Bagga, D., Heber, D., Glaspy, J. A., & Aronson, W. J. (2006). Effect of altering dietary ω-6/ω-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E 2 Clinical Cancer Research, 12(15), 4662-4670. https://doi.org/10.1158/1078-0432.CCR-06-0459