Effects of omega-3 fatty acids on components of the transforming growth factor beta-1 pathway: implication for dietary modification and prevention in ovarian cancer.

OBJECTIVE: We previously demonstrated that omega-3 fatty acids (OM-3FAs) have definitive inhibitory effects on ovarian cancer cell lines. We sought to determine whether the inhibitory effects of OM-3FAs were mediated by the transforming growth factor (TGF)-beta1 signaling pathway. STUDY DESIGN: Ovarian cancer cell lines were grown at 37 degrees C in 5% CO(2) and treated with OM-3FAs, omega-6 fatty acids, and control at different concentrations for 24-72 hours. Enzyme-linked immunosorbent assay (ELISA) assay and Western blot analysis were used to measure TGF-beta1, phosphorylated mothers against decapentaplegic (Smad)-3 and p21 protein levels. RESULTS: An ELISA assay demonstrated that OM-3FA treatment increased TGF-beta1 in all 3 Hey cell lines (P < .05). In both SKOV-3 and OVCAR-3 cells, TGF-beta1 levels were not significantly increased. Western blots confirmed increases in TGF-beta1, Smad-3 and p21 protein levels in Hey and HeyC2 but not SKOV-3 and OVCAR-3 cells. CONCLUSION: OM-3FAs increased the level of TGF-beta1, Smad-3, and p21 protein in ovarian cancer cells known to be more sensitive to their inhibitory effect.

The effects of Omega-3 fatty acids on growth regulation of epithelial ovarian cancer cell lines.

OBJECTIVE: Omega-3 fatty acids (OM-3FAs) have been shown to possess anti-carcinogenic properties. We investigated the effect of OM-3FAs on epithelial ovarian cancer cell lines to determine if a growth suppressive effect existed and to gain a better insight on the potential molecular mechanisms that may be involved. METHODS: Three epithelial ovarian cancer cell lines (SKOV-3 [p53 null], TOV-21G [wt p53] and OVCAR-3 [mutant p53]) and one immortalized ovarian surface epithelial cell line (IOSE-29 [wt p53]) were treated with OM-3FAs and evaluated for cellular proliferation (WST-1 assay), apoptosis (Annexin V-FITC/PI method) and VEGF expression (VEGF ELISA assay). RESULTS: A statistically significant inhibitory effect under the influence of OM-3FAs was detected in all four cell lines. Apoptosis and VEGF down-regulation were either limited or not detected in the p53 null and mutant cell lines, SKOV-3 and OVCAR-3 respectively. Apoptosis and/or VEGF down-regulation was strongly evident in the wt p53 cell lines TOV-21G and IOSE-29. CONCLUSION: These data suggest that, under the influence of OM-3FAs, there are definitive growth suppressive mechanisms at work and that the biologic effects of OM-3FAs may in part be mediated by the p53 status.