gamma-linolenic-acid 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

Eicosatrienoic acid (ETA 5,8,11, n-9) is abnormally increased by essential fatty acid deficiency (EFAD), a condition associated with alterations of cell proliferation and differentiation. In comparison to certain EFAs, addition of ETA at a low concentration resulted in a reduction in the expression of the cell-cell adhesion molecule, E-cadherin, and to a lesser degree, of desmoglein, along with increased invasion of Matrigel by human squamous cell carcinoma (SCC) cells in vitro. At higher concentrations, ETA stimulated the growth of SCC cells. As previously shown, n-6 EFAs (mainly 18:3 n-6, GLA), up-regulated the expression of E-cadherin and desmoglein. This is the first report showing that the abnormal 20:3 n-9 (Mead's acid) is a down regulator of antimetastatic E-cadherin and desmoglein expression.

Topics: 8,11,14-Eicosatrienoic Acid; Bisbenzimidazole; Blotting, Western; Cadherins; Carcinoma, Squamous Cell; Cell Adhesion Molecules; Cell Division; Cytoskeletal Proteins; Desmogleins; Desmoplakins; Dose-Response Relationship, Drug; gamma-Linolenic Acid; Humans; Immunohistochemistry; Tumor Cells, Cultured

The nude mouse human tumour xenograft system was used as an in vivo model to investigate the possible effect of gamma-linolenic acid (GLA) both on established tumour xenografts and as a prophylactic agent prior to tumour induction. Eighty-nine nude mice bearing a range of different human tumours were studied and two solvents (each of which presented certain practical problems) were used to deliver GLA parenterally to the animals. GLA treatment was found to have no significant effect on the growth of any of the tumour xenografts investigated.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Female; gamma-Linolenic Acid; Linolenic Acids; Male; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Transplantation, Heterologous

Cells of two continuous human oesophageal carcinoma lines were treated by the addition of gamma-linolenic acid (GLA) at concentrations of 10-60 micrograms/ml culture medium. After 7 days of exposure to GLA, pronounced morphological changes became evident and culminated in cell death. GLA-mediated effects were time- and dose-dependent and varied slightly with the degree of histological differentiation of the lines tested. These findings may have clinical implications.

Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Cells, Cultured; Dose-Response Relationship, Drug; Esophageal Neoplasms; gamma-Linolenic Acid; Humans; Linolenic Acids; Time Factors