Omega-6 fatty acids can inhibit Fas-mediated apoptosis in a human colorectal carcinoma cell line: a potential mechanism for escape from immune surveillance.
The Fas/Fas ligand pathway may play an important role in the pathogenesis of colorectal carcinoma by allowing tumor cells to evade host immune defenses. Since dietary fats, in particular omega-6 fatty acids, facilitate tumor development their influence on the Fas/Fas ligand pathway needs to be elucidated. The purpose of this study was to determine the effect of membrane free fatty acid (FFA) alterations on Fas expression and sensitivity. Two human colorectal carcinoma cell lines (CX-1 and CCL-188) were grown in cell culture media supplemented with omega-3 (docosahexanoic acid) and omega-6 (linoleic acid) fatty acids. Membrane alterations were confirmed by gas chromatography (GC). Cell surface Fas expression was determined with flow cytometry using an anti-Fas monoclonal antibody. Sensitivity to Fas mediated apoptosis was measured by now cytometric measurement of fragmented DNA stained with propidium iodide. Appropriate changes in the membrane FFA composition were found by GC. Cell surface Fas expression was unaffected in either cell line. Omega-3 fatty acids did not alter Fas sensitivity for either cell line compared to control (CX-1: 59.7%, +/- 5.4 vs 51.4% +/- 7.1 for control, CCL-188: 54.3% +/- 8.6 vs 51.2% +/- 4.8 for control). Omega-6 fatty acids produced a significant decrease in Fas-mediated apoptosis (CX-1: 34.2% +/- 4.8 and CCL-188: 22% +/- 6.0, p < 0.05 vs control). These data indicate that although membrane FFA alterations did not affect Fas expression, omega-6 fatty acids significantly decreased Fas-mediated apoptosis. This inhibitory effect may protect colorectal carcinoma cells from lymphocyte Fas-mediated cell death.
Meterissian
S
S
Department of Surgery, Royal Victoria Hospital, Montreal, Quebec, Canada.
Kontogiannea
M
M
Murty
H
H
Gupta
A
A
D017209:Apoptosis; D015179:Colorectal Neoplasms / Q000473:pathology; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D007157:Immunologic Surveillance; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D004042:Dietary Fats, Unsaturated; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D019014:fas Receptor