Abstract P4-09-02: Omega-3 ethyl esters suppress breast cancer growth by modulating inflammatory signaling

Introduction: Inflammation has been identified as a key contributor to breast cancer development. Both clinical and preclinical studies confirm a role for inflammatory mediators such as cytokines, interleukins, embedded immune cells and prostaglandins in promoting development of breast cancer. Elevated levels/activity of cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) are correlated with a more aggressive disease. Omega-3 fatty acid (n-3) intake is correlated with an inverse risk for breast cancer development and improvement in prognostic markers. One key target of omega-3 fatty acids is the COX-2 enzyme. We hypothesize that one mechanism by which omega-3 fatty acids suppress breast cancer progression is through inhibition of inflammatory signaling. Methods: The impact of omega-3 ethyl esters (n-3 EE), a component of some omega-3 supplements, on the viability of MCF-7 breast cancer cells grown in a pro-inflammatory environment was assessed by MTT analysis and on proliferation by cell counting. Supplementation of the growth media with IL-6 (10ng/mL) was used to simulate a pro-inflammatory environment. Changes in expression levels of key components of inflammatory pathways were assessed by Western blot analyses and quantitative PCR. Prostaglandin E2 (PGE2) levels were measured using ELISA assays. Results: A significant suppression in IL-6-induced proliferation was observed when cells were exposed to physiological concentrations (20 uM) of n-3 EE for 96 hrs. Molecular analyses suggest that the suppression of the NF-kB/COX-2/PGE2 signaling axis was important for mediating this effect. These results are consistent with other studies using specific COX-2 inhibitors. Conclusions: With their potent anti-inflammatory activity, n-3 EE may prove useful in reducing malignancy of breast cancer and also slow development of new breast cancers. Importantly, they appear to have none of the toxicities associated with pharmaceutical COX inhibitors (NSAIDs). Future studies are planned to incorporate nutraceutical compounds to standard therapy to improve efficacy and reduce associated side effects. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-09-02.