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

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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

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Cyclooxygenase 2
Prostaglandins E
Prostatic Neoplasms
Fatty Acids
Omega-3 Fatty Acids
Membranes
Los Angeles
Serum
Neoplasms
Fats
Tumor Burden
Staining and Labeling
Severe Combined Immunodeficiency
Fish Oils
Lipoma
Prostate-Specific Antigen
Tumor Biomarkers
Growth
Transferases
Energy Intake

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Effect of altering dietary ω-6/ω-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E 2 . / Kobayashi, Naoko; Barnard, R. James; Henning, Susanne M.; Elashoff, David; Reddy, Srinivasa T.; Cohen, Pinchas; Leung, Pak; Hong-Gonzalez, Jenny; Freedland, Stephen J.; Said, Jonathan; Gui, Dorina; Seeram, Navindra P.; Popoviciu, Laura M.; Bagga, Dilprit; Heber, David; Glaspy, John A.; Aronson, William J.

In: Clinical Cancer Research, Vol. 12, No. 15, 01.08.2006, p. 4662-4670.

Research output: Contribution to journalArticle

Kobayashi, N, Barnard, RJ, Henning, SM, Elashoff, D, Reddy, ST, Cohen, P, Leung, P, Hong-Gonzalez, J, Freedland, SJ, Said, J, Gui, D, Seeram, NP, Popoviciu, LM, Bagga, D, Heber, D, Glaspy, JA & Aronson, WJ 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, vol. 12, no. 15, pp. 4662-4670. https://doi.org/10.1158/1078-0432.CCR-06-0459
Kobayashi, Naoko ; Barnard, R. James ; Henning, Susanne M. ; Elashoff, David ; Reddy, Srinivasa T. ; Cohen, Pinchas ; Leung, Pak ; Hong-Gonzalez, Jenny ; Freedland, Stephen J. ; Said, Jonathan ; Gui, Dorina ; Seeram, Navindra P. ; Popoviciu, Laura M. ; Bagga, Dilprit ; Heber, David ; Glaspy, John A. ; Aronson, William J. / Effect of altering dietary ω-6/ω-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E 2 In: Clinical Cancer Research. 2006 ; Vol. 12, No. 15. pp. 4662-4670.
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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.",
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AU - Kobayashi, Naoko

AU - Barnard, R. James

AU - Henning, Susanne M.

AU - Elashoff, David

AU - Reddy, Srinivasa T.

AU - Cohen, Pinchas

AU - Leung, Pak

AU - Hong-Gonzalez, Jenny

AU - Freedland, Stephen J.

AU - Said, Jonathan

AU - Gui, Dorina

AU - Seeram, Navindra P.

AU - Popoviciu, Laura M.

AU - Bagga, Dilprit

AU - Heber, David

AU - Glaspy, John A.

AU - Aronson, William J.

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N2 - 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.

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