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- W3129553233 abstract "Background: Recent studies have shown that omega-3 fatty acids can inhibit tumorigenesis. In the present study, we determined in rats the pharmacokinetics and tissue distribution of two major omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), following oral administration of fish oil. In addition, we have also evaluated their anticancer activity against the growth of human MCF-7 breast cancer cells in vitro and also the underlying mechanism. Methods: Male Sprague-Dawley rats (300 g) were used for the pharmacokinetic study. Commercially-available fish oil (2 mL, containing 180 mg/mL EPA and 120 mg/mL DHA) was orally administered to the animals following overnight fasting. Blood was drawn at 1, 2, 3, 4, 5, 8, 12 and 24 h following the fish oil administration. Levels of DHA and EPA in the blood and various tissues (brain, heart, lung, liver, kidney, pancreas, spleen, small intestine and adipose) were determined by using GC-MS. Their anti-breast cancer activity was determined in cultured cells. Results: Brain showed the highest levels of endogenously-produced DHA, and its levels in several other tissues were also higher than EPA. After a single oral administration of fish oil containing both EPA and DHA to rats, the serum levels of EPA and DHA reached its maximum concentrations at 5 h, and the levels were gradually decreased to the original endogenous levels at 12 h after administration. The levels of EPA in the small intestinal tissue were increased by 13-fold, whereas the levels of DHA were increased by 3.4-fold. Similarly, the increase of EPA levels in heart, lung, liver, kidney, pancreas and spleen was also higher than the increase of DHA levels. Anticancer experiments showed that EPA and DHA, when present at endogenously-achievable tissue concentrations, exerted a strong growth-inhibitory effect in MCF-7 human breast cancer cells in culture. Mechanistic studies revealed that an increased formation of reactive free radicals contributed importantly to the anticancer activity of EPA and DHA since the presence of vitamin E strongly protected these cells from undergoing apoptosis. Interestingly, the anticancer effects of EPA and DHA were much weaker in MDA-MB-435s human breast cancer cells under the same conditions. Conclusion:Administration of DHA and EPA through oral intake of fish oil has a relatively short half-life in circulation but favorable distribution in a number of tissues. In addition, both EPA and DHA are highly efficacious in suppressing the growth of certain types of human breast cancer in vitro. More studies are warranted to further explore their potential anticancer and chemopreventive effects in animal models and human subjects. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2916." @default.
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- W3129553233 date "2009-05-01" @default.
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- W3129553233 title "Abstract #2916: Pharmacokinetics, tissue distribution and anticancer activity of eicosapentaenoic acid and docosahexaenoic acid, two cancer chemopreventive omega-3 fatty acids" @default.
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