Abstract B74: Dietary reprogramming of the metabolome of the laying hen: Prevention and suppression of ovarian cancer

Ovarian cancer is the most lethal gynecological malignancy among women in the US and causes 14,600 deaths annually. Unfortunately, despite intensive research towards detection and treatment of ovarian cancer, long term survival has only fractionally improved. Lack of a model animal, early detection, and curative chemotherapy has hampered progress in the fight against ovarian cancer. The laying hen is proving to be a robust model of spontaneous ovarian cancer that mimics human disease. Nutritive intervention with flaxseed, high in omega 3 polyunsaturated fatty acids (PUFA), has shown promise for reducing severity and incidence of ovarian cancer, by reprogramming cellular metabolism, ameliorating inflammatory pathways in comparison with a diet high in omega 6 PUFA, such as corn oil. We have demonstrated that omega 3 fatty acids and phytoestrogens lignans has greatly reduced cancer incidence and severity in the laying hen by targeting inflammatory pathways. Another finding from our flaxseed feeding study, is that the overall wellbeing of the hens was also improved by the diet. Mortality was significantly reduced and the lean body mass of the hens was improved and maintained. The objective of this study was to determine if 6 different diets consisting of: control meal, defatted flax meal, whole flax seed, corn oil, fish oil, and flax oil affect the plasma metabolomics profile compared to a control diet, hence contributing to their anti and pro-carcinogenic effects on ovarian cancer. Old, cancer prone hens were fed a diet for one year, after 6 months, blood was collected through wing vein, plasma was prepared. Samples were snap frozen within 5 minutes or less of collection. Plasma was subjected to one-carbon base metabolomics analysis at UT Southwestern by Ralph DeBerardinis and Zeping Hu. Discovery based metabolomic analysis results indicate that a host of differences among 125 metabolites were found. 63% of the variability in the metabolites can be accounted for by the 6 diets. The analysis indicates that there are suites of metabolites associated with the different dietary treatments. Principal component analysis and hierarchal clustering revealed within the flax fed group urea, hypoxanthine adenosine, and myo-inositol metabolites increased compared to the control diet. This could be indicative of a protective effect. Conversely, homoserine, lysine, methionine, and sulfoxide were decreased in the flax diet compared to the control diet. Hens fed a corn oil diet gave rise to an increase in homoserine, lysine, methionine sulfoxide metabolites compared to the control diets, which has been associated with systemic oxidative stress. Also with the corn oil diet, a decrease in the concentration of urea, hypoxanthine, adenosine, and myo-inositol metabolites was observed, compared to the control diet. Interestingly, it has been previously reported that a reduction in these metabolites has been observed from patients with non-Hodgkin Lymphomas. The changes in the concentration of metabolites are suspected to be the result of the diet-driven alterations in surrogate cancer endpoints. To further map observable changes in the metabolic profile of tumor metabolism, analysis of tissue level metabolites will be assessed next with emphasis on malignant tissue versus normal tissues within the respective diets. [Supported by NIH AT004085, AT005295] Citation Format: Stephanie M. Eastwood, Lacey Gibson, Dale Buchanan Hales. Dietary reprogramming of the metabolome of the laying hen: Prevention and suppression of ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B74.