Breast cancer is the most prevalent cancer and the second most common cause of cancer death in women in the United States. This dissertation focuses on the study of food processing modulation on breast cancer in two separate studies.First, the soy processing effect on breast cancer was investigated. Soy flour diet (MS) prevented isoflavones from stimulating MCF-7 tumor growth in athymic nude mice, indicating that other bioactive compounds in soy can negate the estrogenic properties of isoflavones. The underlying signal transduction pathways to explain the protective effects of soy flour consumption were studied. Ovariectomized athymic nude mice inoculated with MCF-7 human breast cancer cells were fed either MS or purified isoflavone mix (MI), both with equivalent amounts of genistein. Positive controls received estradiol pellets and negative controls received sham pellets. GeneChip Human Genome U133 Plus 2.0 Array platform was used to evaluate gene expression, and results were analyzed using bioinformatics approaches. Tumors in MS-fed mice exhibited higher expression of tumor growth suppressing genes ATP2A3 and BLNK, and lower expression of oncogene MYC. Tumors in MI-fed mice expressed higher level of oncogene MYB and lower level of MHC-I and MHC-II, allowing tumor cells to escape immunosurveillance. MS-induced gene expression alterations were predictive of prolonged survival among estrogen receptor positive breast cancer patients, whilst MI-induced gene changes were predictive of shortened survival. Our findings suggest dietary soy flour affects gene expression differently than purified isoflavones, which may explain why soy foods prevent isoflavones-induced stimulation of MCF-7 tumor growth in athymic nude mice. Future study will be conducted to characterize the composition of the bioactive components other than isoflavones in the soy flour diet, and their anticipated protective effects on breast cancer growth.Second, the link between the physical and chemical characteristics of moderately ther- mally abused oil (TAO) and their relevance to the biological responses in breast cancer metastasis was examined. Deep-frying is a popular food processing method worldwide. The intake of fried foods accounts for approximately 15% of the total calorie intake in industrialized countries, which is more than half of energy intake originating from fat. Mounting evidence suggest that a high fat diet has a substantial impact on cancer. However, the relationship between deep-fried food intake and breast cancer development remains unclear. In fact, although individual latent undesirable compounds produced during deep- frying have been shown to be carcinogenic, little is known about their impacts on breast cancer in a whole food system. In this study, soybean oil was thermally abused and time series data were collected. Three different foods including potato strips, chicken strips and catfish nuggets were fried. The physical (color and viscosity) and chemical changes (peroxide value, p-anisidine value, free fatty acid, polar component, fatty acid composition) of TAO were characterized at different time points. Repeated exposure to high temperature, led to significant deterioration of oil and accumulation of high concentration of undesirable compounds. This process resulted in food-dependent changes, in the order of fish TAO > chicken TAO > potato TAO. Most importantly, the deterioration of and undesirable component formation in TAO positively correlated with breast cancer metastasis in the preclinical model. This is the first study to investigate the causal link between thermally abused oil characteristics and its direct negative biological responses in a preclinical model of breast cancer. Future studies will be continued to characterize the undesirable components in TAO, such as epoxy- fatty acids and cyclic fatty acids. Additional preclinical studies need to be conducted to confirm that consumption of diets high in TAO induces more aggravated breast cancer metastasis than diets low in TAO. More importantly, fried food can be further incorporated into the diet, to verify the adverse impact of consuming food fried in TAO.
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