Abstract B60: Exploitation of a common food/traditional medicine of South America, yacon, in breast cancer prevention in the U.S. using preclinical rat model

Background: Yacon has recently been introduced into farmer9s markets and natural food stores in the U.S., but its preventive activity for breast cancer has rarely been evaluated. Yacon contains a large amount of non-digestible oligosaccharide called inulin that belongs to a class of carbohydrates known as fructans. Inulin-type fructans (ITF) decreases the rate of aberrant crypt foci (ACF), a pre-neoplastic lesion found in colon. The mechanism by which ITF inhibits ACF is associated with butyrate produced by the anaerobic bacterial fermentation of ITF in the colon. Butyrate can also be absorbed through the colonic epithelial cells into the portal blood and exert its effects within the body. Butyrate modulates gene transcription by inhibiting HDAC. Cancer cells appear to be more sensitive than non-transformed cells to HDAC inhibitory compounds. In addition, the yacon ITF promotes satiety and retard the absorption of food-derived energy via reducing a gastrointestinal peptide-ghrelin that is a growth hormone secretagogue. Reduction of serum ghrelin results in decreases of IGF-1. Subsequently, the PI3K/Akt-mTOR signaling pathway will be inactivated via increasing AMPK activity and its downstream events, inhibition of cell proliferation and induction of cell apoptosis. However, few studies have been shown the effect of the ITF on breast cancer. Objective: 1) To determine mammary carcinogenic responses to yacon in experimental animals; 2) To evaluate the association of the circulating growth factors and cytokines with the carcinogenic responses; 3) To determine the HDAC and identify AMPK/PI3K/Akt-mTOR cell signaling pathway. Methods: Mammary carcinogenesis was initiated by injection of female Sprague Dawley rats with 50 mg of 1-methyl-1-nitrosourea/kg body weight (i.p.) at 21 days of age. One week later, the rats were fed diets containing yacon powder at 0%, 15%, 30% or 60% (30 rats/group) for 8 weeks, respectively. Effects of yacon on mammary carcinomas, circulating growth factors and cytokines and molecular biological assessments in carcinomas, including HDAC and regulators that are associated with AMPK/PI3K/Akt-mTOR pathway, were evaluated. Difference between among different dietary groups was statistically analyzed by ANOVA and Chi-square test. Results/Relevance: Dietary yacon reduced the promotion and progression of MNU-induced mammary carcinogenesis in rat, which is associated with downregulation of IGF-1/HDAC/Akt/mTOR signaling pathway and anti-inflammation, i.e. reduction of plasma IL-6, TNFα, and C-reactive protein. Future work will focus on the effect of yacon on obesity and antiinflammation. The study provides crucial biological information to complement the knowledge of natural functional foods that is relevant to a number of foods rich in non-digestible, fermentable oligosaccharides. This could lead the way to develop a new type of functional whole food with a low calorie density and the ability to promote the intra-intestinal production of cancer inhibitory factors. Consequently, the new type of functional food will significantly contribute to the goal of preventing initiation of breast cancer and reduce survivor recurring because it is natural, tolerant and acceptable for the clinic patients. Supported by W81XWH-09-1-0428 from the Department of Defense-Army. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B60.