The effects of exogenous
gamma-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 55 kDa (approximately 55 kDa) was primarily influenced in both WHCO3 and WHCO1.
PGA2 caused a decrease in
tyrosine phosphorylation of the approximately 55 kDa
protein in all three cell types. Negligible differences were observed in the
tyrosine phosphorylation status of the approximately 55 kDa in NMK cells exposed to GLA, AA and
PGE2 respectively. However,
tyrosine phosphorylation of a number of other
proteins (21.5-97.4 kDa) was observed in NMK cells. Flow cytometry studies showed an increase in S phase and decrease in G1 phase in WHCO3 exposed to
PGE2 and
PGA2.
Indomethacin alone, or in combination with GLA and AA, respectively, lead to an increase in G1 and 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.