Omega-3 Fatty Acids Induce TGF-beta Ova Ca

Omega-3 fatty acids induce TGF-1 expression in epithelial ovarian cancer

Arun Sharma, Jennifer Belna, Jennifer Logan, Jean Hurteau. University of Illinois, Chicago, IL.

Background: Ovarian cancer is often asymptomatic in its early stages and most patients have widespread disease at the time of diagnosis. Epithelial ovarian cancer is the most common form of ovarian cancer with a long-term survival rate of approximately 30%. Measures used to prevent this disease are somewhat invasive or have the potential for significant side effects.

Omega-3 fatty acids (OM-3FAs) are a non-toxic supplement that we have previously shown to reduce the proliferative capacity of immortalized epithelial ovarian cancer cell lines accompanied with the down-regulation of pro-angiogenic molecules, such as VEGF.

In this study, we show that OM-3FAs also have the ability to up-regulate the pleiotropic anti-proliferative molecule TGF-1 in vitro.

Aim: To study the effects of OM-3FAs as a possible non-toxic chemo-preventative/treatment modality for epithelial ovarian cancer through the TGF-1 signaling pathway. Methods: 8x106 cells/T75 flask of the epithelial ovarian cancer cell lines OVCAR3, SKOV3, Hey, HeyC2, and HeyA8 were plated in appropriate culture media and incubated at 370C at 5% CO2 overnight.

An OM-3FA emulsion (or control media alone) at either 100M or 150M was then added to corresponding flasks and incubated from 24-72 hrs at 24hr increments. An ELISA assay for TGF-1 (RandD Systems, MN) was then performed according to manufacturers instructions.

Results: After treatment with the OM-3FA emulsion, TGF-1 expression was dramatically up-regulated in the following manner: Hey cell line was 7% greater than control at 24hrs and 32% greater than control at 48hrs with 150M OM-3FAs; HeyA8 cell line was 17% greater than control at 24hrs and 33% greater than control at 48hrs with 100M OM-3FAs; HeyC2 cell line was 8% greater than control at 48hrs and was 35% greater than control at 72hrs with 100M OM-3FAs.

SKOV3 cell line was 5% greater than control at 72hrs with 150M OM-3FAs. TGF-1 expression was not effected in the OVCAR3 cell line (n=3). Conclusion: OM-3FAs have recently been shown to reduce the carcinogenic potential in a number of different cancers.

Although a mechanism of action has not been delineated, one know molecule, TGF-1, acts as a key molecule for cellular growth inhibition with anti-angiogenic capabilities. By studying the effects of OM-3FA on epithelial ovarian cancer cells, we have demonstrated that OM-3FAs can induce expression of TGF-1from 5-33% greater than a control population further limiting the growth potential of these epithelial ovarian cell lines in vitro.

This data further suggests that there are definitive growth suppressive mechanisms that may play a role in the down regulation of other molecular pathways that are responsible for uncontrolled cellular proliferation.

Ongoing studies will address the anti-angiogenic effects of TGF-1 through the SMAD family of proteins and thrombospondin receptor signaling pathways.

AACR 2005 Abstract #6091

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