title: Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids.
abstract: Although a causal role of genetic alterations in human cancer is well established, it is still unclear whether dietary fat can modulate cancer risk in a predisposed population. Epidemiological studies suggest that diets rich in omega-3 polyunsaturated fatty acids reduce cancer incidence. To determine the influence of fatty acids on prostate cancer risk in animals with a defined genetic lesion, we used prostate-specific Pten-knockout mice, an immune-competent, orthotopic prostate cancer model, and diets with defined polyunsaturated fatty acid levels. We found that omega-3 fatty acids reduced prostate tumor growth, slowed histopathological progression, and increased survival, whereas omega-6 fatty acids had opposite effects. Introducing an omega-3 desaturase, which converts omega-6 to omega-3 fatty acids, into the Pten-knockout mice reduced tumor growth similarly to the omega-3 diet. Tumors from mice on the omega-3 diet had lower proportions of phosphorylated Bad and higher apoptotic indexes compared with those from mice on omega-6 diet. Knockdown of Bad eliminated omega-3-induced cell death, and introduction of exogenous Bad restored the sensitivity to omega-3 fatty acids. Our data suggest that modulation of prostate cancer development by polyunsaturated fatty acids is mediated in part through Bad-dependent apoptosis. This study highlights the importance of gene-diet interactions in prostate cancer.
authors.affiliation: Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Berquin
authors.forename: Younong
authors.initials: Y
authors.lastname: Min
authors.forename: Ruping
authors.initials: R
authors.lastname: Wu
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Wu
authors.forename: Donna
authors.initials: D
authors.lastname: Perry
authors.forename: J Mark
authors.initials: JM
authors.lastname: Cline
authors.forename: Mike J
authors.initials: MJ
authors.lastname: Thomas
authors.forename: Todd
authors.initials: T
authors.lastname: Thornburg
authors.forename: George
authors.initials: G
authors.lastname: Kulik
authors.forename: Adrienne
authors.initials: A
authors.lastname: Smith
authors.forename: Iris J
authors.initials: IJ
authors.lastname: Edwards
authors.forename: Ralph
authors.initials: R
authors.lastname: D'Agostino
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D018450:Disease Progression; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism / Q000494:pharmacology*; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology*; D015996:Survival Rate; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: C494820:Bad protein, mouse; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D051025:bcl-Associated Death Protein; D051059:PTEN Phosphohydrolase