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

Am J Obstet Gynecol. 2009 May;200(5):516.e1-6. doi: 10.1016/j.ajog.2008.12.023. Epub 2009 Mar 9.

Abstract

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.

MeSH terms

  • Benzamides
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Fatty Acids, Omega-3 / pharmacology*
  • Fatty Acids, Omega-6 / pharmacology
  • Female
  • Humans
  • Ovarian Neoplasms / diet therapy
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / prevention & control*
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects*
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Benzamides
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • SMAD3 protein, human
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • Tumor Suppressor Protein p53
  • isoxaben