Omega-3 and breast cancer : the role of NF-κB and CCL20 in treating and preventing breast cancer
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High intakes of omega-3 fatty acids are associated with a lower risk of breast cancer. The risk for breast cancer is three times lower in women who frequently supplement their diets with omega-3 fatty acids. In vitro experiments have studied the molecular mechanisms by which omega-3 fatty acids reduce breast cancer viability but much remains unclear to how omega-3 ethyl esters, a main component of omega-3 prescription and supplementation, prevent breast cancer. This study utilizes the prescription drug Lovaza® as the source of omega-3 ethyl esters and tests its efficacy in treating an array of breast cancer cell lines. One of the many purposes of this study is to identify the working pathways omega-3 ethyl esters modulate to elicit anti-cancer effects and to identify a potential biomarker that may correlate with response. Four in vitro breast cancer cell lines were utilized to comprise a diverse genetic platform for the testing of Lovaza® derived omega-3 ethyl esters. This diversity led to the identification of a potential biomarker that may be used to predict response to omega-3 ethyl esters. Among the four breast cancer cell lines, the expression and over-activation of NF-κB correlated with a favorable response. The regulation of NF-κB and its activity was one of the key mechanisms through which omega-3 ethyl esters suppressed breast cancer cell survival and viability. Future validation of this biomarker is warranted and may be useful for clinical development. In addition to the four breast cancer cell lines, a set of precancerous breast cells was utilized for the preventive study in this dissertation. This set of three human breast cell lines display characteristics of hyperplasia, Ductal Carcinoma In Situ (DCIS) and invasive mammary carcinoma in vivo and characterization of these cell lines showed over expression of the CCL20 cytokine and over activation of the Wnt signaling pathway. Docosahexaenoic acid (DHA), a form of omega-3 fatty acids, was examined in these cell lines for its efficacy to prevent breast cancer. DHA was supplemented into growth media and cells were evaluated for survival, proliferation, invasion and cytokine production. CCL20 cytokine production was reduced and ERK1/2 and AKT signaling pathway suppression played an important role in DHA mediated suppression of survival and proliferation. Additional studies determining the effect of DHA on cell invasion were also conducted.