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.


METHODS
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.


CONCLUSIONS
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.
Sharma
Arun
A
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Illinois Medical Center at Chicago, Chicago, IL, USA.
Belna
Jennifer
J
Espat
Joseph
J
Rodriguez
Gustavo
G
Cannon
Vernon T
VT
Hurteau
Jean A
JA
D001549:Benzamides; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000178:diet therapy / Q000378:metabolism* / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D001549:Benzamides; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53; C057467:isoxaben