Abstract 1816: Effects of high ω-3 fatty acid diet on prostate tumorigenesis in C3(1) Tag mice

Abstract Epidemiological studies have shown that intake of diet high in omega 6 polyunsaturated fatty acid (ω-6 PUFA) increases the risk of prostate cancer while the diet high in omega-3 polyunsaturated fatty acid (ω-3 PUFA) decreases the risk. Omega-6 PUFA are abundant in corn oil and sunflower oil while omega-3 PUFA are abundant in fish oil, canola oil and walnut. Both ω-6 and ω-3 play an important role in prostate cancer risk. Prostate cancer incidence and mortality are high in the Western world and high ω-6/ ω-3 PUFA in the Western diet may be a contributing factor. The aim of this study was to investigate whether a change from a diet that approximates the ω-6 fatty acid content of the Western diet to a high ω-3 fatty acid diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing 10% w/w corn oil (containing 50% ω-6 and 1% ω-3) for two weeks were bred with homozygous C3(1) Tag transgenic male mice. All male offspring (hemizygous) were weaned to the corn oil diet and consumed this diet until post puberty (7 weeks). Since the aim of the study was to simulate a diet change at adulthood, half of the male offspring were transferred to a high ω-3 diet containing 5%w/w canola oil and 5% w/w fish oil concentrate (containing 1%w/w ω-6 and 35%w/w ω-3). The male hemizygous mice were euthanized at age 24wks and 40wks (end of reproduction). Gas chromatography was used to assess the fatty acid composition in the prostate, liver and fat tissues. Enzyme-linked immunoassay was used to assess the levels of testosterone and estradiol in blood plasma. RT2 PCR and WB analyses were used to assess mRNA gene and protein expression respectively in the dorsalateral (DL) prostate. The results demonstrated that high ω-3 diet increased the ALA, EPA and DHA and decreased the LA and AA content of the prostate, liver and fat tissues. The average weights of prostate and genitourinary bloc (GU block) at 24 wks and 40 wks were significantly lower in mice that consumed the high ω-3 diet at adulthood (CO-FS) than in mice that consumed the high ω-6 diet (CO-CO) throughout life. Compared to mice in CO-CO group, CO-FS mice had lower plasma testosterone level at 24wks and 40wks, and significantly lower estradiol level at 40wks. Gene expression analyses showed that consumption of high ω-3 diet altered expression of genes that would be expected to slow proliferation and increase apoptosis in the DL prostate. Our findings suggest that if adult consume high ω-3 (but low in ω-6) diet, it may be useful in the suppression and prevention of prostate cancer. Further ongoing investigation include pathological evaluation of DL prostate from the two diet groups and immunohistochemical analyses to assess the expression of AR, ER and proliferation in the mice DL prostate. TUNEL assay will be used to assess apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1816. doi:10.1158/1538-7445.AM2011-1816