Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2.
OBJECTIVE
To determine whether altering the dietary content of omega-6 (n-6) and omega-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 E(2) (PGE(2)) levels.


METHODS
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.


CONCLUSIONS
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.
Kobayashi
Naoko
N
Department of Urology, Division of Clinical Nutrition and Hematology-Oncology, University of California, Los Angeles School of Medicine, 90095-1738, USA.
Barnard
R James
RJ
Henning
Susanne M
SM
Elashoff
David
D
Reddy
Srinivasa T
ST
Cohen
Pinchas
P
Leung
Pak
P
Hong-Gonzalez
Jenny
J
Freedland
Stephen J
SJ
Said
Jonathan
J
Gui
Dorina
D
Seeram
Navindra P
NP
Popoviciu
Laura M
LM
Bagga
Dilprit
D
Heber
David
D
Glaspy
John A
JA
Aronson
William J
WJ
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D004032:Diet; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000032:analysis / Q000494:pharmacology; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage* / Q000032:analysis / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000178:diet therapy* / Q000473:pathology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D015232:Dinoprostone