prostaglandin-a2 and Carcinoma--Squamous-Cell

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.

Topics: Animals; Arachidonic Acid; Carcinoma, Squamous Cell; Cell Division; Cell Line; Chlorocebus aethiops; Dinoprostone; Esophageal Neoplasms; Fatty Acids, Unsaturated; Flow Cytometry; gamma-Linolenic Acid; Humans; Kidney; Phosphorylation; Prostaglandins A; Protein-Tyrosine Kinases; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Tyrosine

Four cyclopentenone prostaglandins (CPPGs) and PGE2 caused significant dose-dependent inhibition in growth of human oral squamous carcinoma cells (SCC-15). The rank order of their potency was PGJ2>PGA1>16, 16-dimethyl PGA1>PGA2>PGE2. In a follow-up experiment it was found that the mean per cent inhibition in cell growth by PGJ2 and delta12-PGJ2 at 10(-5) M was 61.22 and 63.81, while that of 5-fluorouracil and methotrexate was 36.67 and 38.86, respectively. delta12-PGJ2 and PGJ2 induced significant dose-dependent inhibition in nuclear DNA synthesis (i.e. cell proliferation). Combining vitamin E succinate with lower concentrations of CPPGs enhanced significantly their inhibitory effect on nuclear DNA synthesis of cancer cells.

Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Division; Dinoprostone; Fluorouracil; Humans; Methotrexate; Mouth Neoplasms; Prostaglandin D2; Prostaglandins A; Prostaglandins A, Synthetic; Prostaglandins, Synthetic; Tocopherols; Tumor Cells, Cultured; Vitamin E