Long chain PUFAs Omega-3 incorporation in cell membrane microdomains of breast cancer cells

Long chain PUFAs are important molecules for membrane order and function; they can also modify inflammation-inducible cytokines production, regulation of eicosanoid production, plasma TAG synthesis, blood pressure, and gene-expression. Furthermore omega-3 have been hypothesized to influence colorectal carcinogenesis through many mechanisms (e.g. inhibiting COX2, increasing apoptosis, reducing angiogenesis). In breast cancer, supplementation with DHA synergistically enhances taxane cytotoxicity, down regulate HER-2/neu (c-erbB-2) oncogene expression, modifies the production of the heparansulfate syndecan1, suggesting a gene-nutrient interaction of critical importance for mammary carcinogenesis and supporting the hypothesis that omega-3 can be used as modulators of cancer cell chemo-sensitivity. Aim of the study was to evaluate the effects of supplementation of AA, EPA and DHA in two lines of human breast cancer cells characterized by different expression of ER receptor. Moreover we would like to study the fatty acid pattern in membrane phospholipids when they are incorporated with different specificity. After treatments fatty acids are partially metabolized from both cell lines. In particular EPA is promptly converted to DPA,; DHA is partially re-converted in EPA while AA is integrated without being further metabolized. However both omega-3 fatty acids induced cell apoptosis, with different degree and sensitivity, while AA increased cell proliferation in both cell lines. Ongoing we are investigating the role of membrane changes induced by omega-3 fatty acid in micro domain function and signal transduction related to cancer cell proliferation.