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- Title
Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids.
- Authors
Berquin, Isabelle M; Min, Younong; Wu, Ruping; Wu, Jiansheng; Perry, Donna; Cline, J Mark; Thomas, Mike J; Thornburg, Todd; Kulik, George; Smith, Adrienne; Edwards, Iris J; D'Agostino, Ralph; Zhang, Hao; Wu, Hong; Kang, Jing X; Chen, Yong Q
- 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.
- Publication
The Journal of clinical investigation, 2007, Vol 117, Issue 7, p1866
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI31494