Inhibition of the synthesis of eicosanoid-like substances in a human oral cancer cell line by interferon- γ and eicosapentaenoic Acid

Abstract

The objectives were to examine the production of eicosanoids in a Chinese human oral cancer cell line (OEC-M1) and to test the effects of interferon- γ (IFN- γ), eicosapentaenoic acid (EPA) and enzyme inhibitors on this biosynthesis. The eicosanoids were identified by reverse phase-high performance liquid chromatography. Two predominant peaks appeared in the chromatograms. One compound (P-1) was identified by ultraviolet absorption at a λ max of 278 nm with shoulders at 272 and 284 nm. The other compound (P-2) was identified by ultraviolet absorption at a λ max of 284 nm with shoulders at 278 and 290 nm. The production of P-1 was significantly inhibited by the addition of IFN- γ (200 and 400 U/ml), and EPA (10 to 40 μM). It was only partially inhibited ( p<0.05) by indomethacin (INDO) (0.5 and 1 μM), nordihydroguaiaretic acid (NDGA) (30 and 60 μM/ml), and eicosa-5,8,11,14-tetraynoic acid (ETYA) (20–60 μM). It was almost completely inhibited by indomethacin (2 and 3 μM), and dexamethasone (0.6 and 6 μM). The production of P-2 was almost completely inhibited by IFN- γ (200 and 400 U/ml), and partially inhibited ( p<0.05) by EPA (10 and 20 μM), NDGA (30 and 60 μM), ETYA (20 and 40 μM), dexamethasone (0.6 and 6 μM). The production of both peaks was significantly reduced by excluding arachidonic acid (AA), and almost completely inhibited by heating at 100°C for 10 min during incubation. These results demonstrate that two eicosanoid-like compounds are synthesized by the OEC-M1 cell line and that their production can be modulated by IFN- γ, EPA, indomethacin, NDGA, ETYA, and dexamethasone.