title: Effect of a low-fat fish oil diet on proinflammatory eicosanoids and cell-cycle progression score in men undergoing radical prostatectomy.
abstract: We previously reported that a 4- to 6-week low-fat fish oil (LFFO) diet did not affect serum insulin-like growth factor (IGF)-1 levels (primary outcome) but resulted in lower omega-6 to omega-3 fatty acid ratios in prostate tissue and lower prostate cancer proliferation (Ki67) as compared with a Western diet. In this post hoc analysis, the effect of the LFFO intervention on serum pro-inflammatory eicosanoids, leukotriene B4 (LTB4) and 15-S-hydroxyeicosatetraenoic acid [15(S)-HETE], and the cell-cycle progression (CCP) score were investigated. Serum fatty acids and eicosanoids were measured by gas chromatography and ELISA. CCP score was determined by quantitative real-time reverse transcriptase PCR (RT-PCR). Associations between serum eicosanoids, Ki67, and CCP score were evaluated using partial correlation analyses. BLT1 (LTB4 receptor) expression was determined in prostate cancer cell lines and prostatectomy specimens. Serum omega-6 fatty acids and 15(S)-HETE levels were significantly reduced, and serum omega-3 levels were increased in the LFFO group relative to the Western diet group, whereas there was no change in LTB4 levels. The CCP score was significantly lower in the LFFO compared with the Western diet group. The 15(S)-HETE change correlated with tissue Ki67 (R = 0.48; P < 0.01) but not with CCP score. The LTB4 change correlated with the CCP score (r = 0.4; P = 0.02) but not with Ki67. The LTB4 receptor BLT1 was detected in prostate cancer cell lines and human prostate cancer specimens. In conclusion, an LFFO diet resulted in decreased 15(S)-HETE levels and lower CCP score relative to a Western diet. Further studies are warranted to determine whether the LFFO diet antiproliferative effects are mediated through the LTB4/BLT1 and 15(S)-HETE pathways.
authors.affiliation: Department of Urology, University of California-Los Angeles, Box 951738, Los Angeles, CA 90095-1738; waronson@ucla.edu.
authors.forename: Colette
authors.initials: C
authors.lastname: Galet
authors.forename: Kiran
authors.initials: K
authors.lastname: Gollapudi
authors.forename: Sevan
authors.initials: S
authors.lastname: Stepanian
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Byrd
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Henning
authors.forename: Tristan
authors.initials: T
authors.lastname: Grogan
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: David
authors.initials: D
authors.lastname: Heber
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.forename: William J
authors.initials: WJ
authors.lastname: Aronson
mesh_terms: D000368:Aged; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018752:Diet, Fat-Restricted; D018450:Disease Progression; D015777:Eicosanoids / Q000097:blood*; D005227:Fatty Acids / Q000097:blood; D005395:Fish Oils / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D007249:Inflammation; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*; D018102:Receptors, Leukotriene B4 / Q000378:metabolism
chemical_list: D015777:Eicosanoids; D005227:Fatty Acids; D005395:Fish Oils; D006893:Hydroxyeicosatetraenoic Acids; D019394:Ki-67 Antigen; C513240:LTB4R protein, human; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D007334:Insulin-Like Growth Factor I; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid