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: Isabelle M Berquin, Younong Min, Ruping Wu, Jiansheng Wu, Donna Perry, J Mark Cline, Mike J Thomas, Todd Thornburg, George Kulik, Adrienne Smith, Iris J Edwards, Ralph D'Agostino, Hao Zhang, Hong Wu, Jing X Kang, Yong Q Chen
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 117 Issue 7 Pg. 1866-75 (Jul 2007) ISSN: 0021-9738 [Print] United States
• PMID: 17607361 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Bad protein, mouse
• Fatty Acids, Omega-3
• Fatty Acids, Omega-6
• bcl-Associated Death Protein
• PTEN Phosphohydrolase

Topics

• Animals
• Apoptosis
• Disease Progression
• Fatty Acids, Omega-3 (metabolism, pharmacology)
• Fatty Acids, Omega-6 (metabolism, pharmacology)
• Gene Deletion
• Genetic Predisposition to Disease
• Male
• Mice
• Mice, Transgenic
• PTEN Phosphohydrolase (deficiency, genetics, metabolism)
• Phosphorylation
• Prostatic Neoplasms (diet therapy, genetics, pathology)
• Survival Rate
• bcl-Associated Death Protein (metabolism)