Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids.

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:
  • The Journal of clinical investigation

دوره 117 7  شماره 

صفحات  -

تاریخ انتشار 2007