Comparative study of the effects of polyunsaturated fatty acids and their metabolites on cell growth and tyrosine kinase activity in oesophageal carcinoma cells

The effects of exogenous γ-linolenic acid (GLA), arachidonic acid (AA), prostaglandin E2(PGE2) and prostaglandin A2(PGA2) were evaluated on cell growth in two squamous oesophageal carcinoma cell lines, WHCO1 and WHCO3 and normal monkey kidney (NMK) cells. In both cancer cell lines all four compounds inhibited cell growth significantly. Indomethacin (I) alone, or in combination with either GLA or AA, caused marked inhibition of cell growth in WHCO3. Total tyrosine kinase (TK) activity was determined after exposure of all three cell types to the lipid compounds. Negligible differences were observed in TK activity between treated and untreated NMK cells. Small increases were noticed in WHCO1. Marked TK stimulation was observed in WHCO3. Addition of indomethacin to WHCO3 also increased TK activity above control value. Tyrosine phosphorylation status of exposed cells indicated that a band of approximately 55kDa (55kDa) was primarily influenced in both WHCO3 and WHCO1. PGA2caused a decrease in tyrosine phosphorylation of the 55kDa protein in all three cell types. Negligible differences were observed in the tyrosine phosphorylation status of the 55kDa in NMK cells exposed to GLA, AA and PGE2respectively. However, tyrosine phosphorylation of a number of other proteins (21.5-97.4kDa) was observed in NMK cells. Flow cytometry studies showed an increase in S phase and decrease in G1 phase in WHCO3 exposed to PGE2and PGA2. Indomethacin alone, or in combination with GLA and AA, respectively, lead to an increase in G1and a decrease in S phase. Induction of p53 levels was observed in WHCO3 cells exposed to GLA, AA, PGA2, indomethacin and the combination of indomethacin and GLA or AA.