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Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids
Isabelle M. Berquin, … , Jing X. Kang, Yong Q. Chen
Isabelle M. Berquin, … , Jing X. Kang, Yong Q. Chen
Published July 2, 2007
Citation Information: J Clin Invest. 2007;117(7):1866-1875. https://doi.org/10.1172/JCI31494.
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Research Article Oncology

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

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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 Jr., Hao Zhang, Hong Wu, Jing X. Kang, Yong Q. Chen

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Figure 1

Suppression of prostate tumor proliferation by omega-3 PUFAs in vivo.

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Suppression of prostate tumor proliferation by omega-3 PUFAs in vivo.
Pt...
PtenP+/+, PtenP+/–, and PtenP–/– mice were fed the high–omega-3, low–omega-3, and high–omega-6 diet for a period of up to 24 weeks. Mouse AP, DL, and VP lobes were weighed, and the sums were expressed as milligrams per 25 gram body weight. Five mice were used per data point in a cohort of 180 mice. Open circles represent mice on the high–omega-3 diet; shaded squares, mice on the low–omega-3 diet; filled triangles, mice on the high–omega-6 diet. Horizontal bars represent averages. SDs are shown for PtenP–/– mice fed with the high–omega-3 and high–omega-6 diet.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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