gamma-linolenic-acid and Liver-Neoplasms

The cytostatic effects of essential fatty acid metabolic intermediates and of some prostaglandins and leukotrienes in vitro have been extensively documented. The essential fatty acids (EFAs) exhibit no side-effects when taken as a dietary supplement, even in large doses. Primary Liver Cancer (PLC) is a fatal disease in our area as it is always multifocal in nature. In vitro studies have shown a cytostatic effect of gamma-linolenic acid (GLA) on primary liver cancer cells. In a double-blind placebo controlled trial, using Evening Primrose Oil (as a source of GLA) as a dietary supplement in PLC patients, no statistically significant effect was observed on survival time or liver size. There was however a statistical significant beneficial effect on Gamma Glutamyl transferase values as a measure of liver function. No side-effects were observed. The large size of tumour and the low doses of GLA used in this trial probably explain the lack of significant effect on survival times.

Topics: Antineoplastic Agents; Clinical Trials as Topic; Double-Blind Method; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; In Vitro Techniques; Linoleic Acids; Linolenic Acids; Liver Neoplasms; Oenothera biennis; Plant Oils; South Africa; Survival Analysis

Topics: Administration, Oral; Adult; Aged; Antineoplastic Agents; Carcinoma, Hepatocellular; Child; Clinical Trials as Topic; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Liver Neoplasms; Male; Mesothelioma; Middle Aged; Neoplasms; Oenothera biennis; Pilot Projects; Plant Oils; Pleural Neoplasms

We examined the influence of diets supplemented with fish and vegetable oils on fatty acid and prostaglandin E2 (PGE2) contents in livers of non-7,12-dimethylbenz[a]anthracene (DMBA)- and DMBA-treated rats, and in DMBA-induced tumours. Decreased concentrations of saturated fatty acids and increased unsaturated fatty acid levels were observed in liver phospholipids of rats fed these oils. There was a marked difference in the concentrations of fatty acids found in the tumours and those present in liver lipids. Oleic acid was the main unsaturated fatty acid found in the tumour tissue. Both liver and tumour PGE2 contents were clearly correlated to the diet. The PGE2 concentrations were decreased in livers and tumours of rats fed fish (FO) and linseed oils (LO).

Topics: 9,10-Dimethyl-1,2-benzanthracene; Analysis of Variance; Animals; Dietary Fats, Unsaturated; Dinoprostone; Fatty Acids; Fatty Acids, Essential; Female; Fish Oils; gamma-Linolenic Acid; Linoleic Acids; Linseed Oil; Liver; Liver Neoplasms; Oenothera biennis; Phosphatidylcholines; Phosphatidylethanolamines; Plant Oils; Rats; Rats, Sprague-Dawley

Incorporation and metabolism of gamma-linolenic acid (GLA) in both rat hepatocytes and Hep G2 cells were compared to those of oleic (OA), linoleic (LA), alpha-linolenic (LLA), and dihomo-gamma-linolenic (DGLA) acids. The incorporation of GLA into both types of cells was higher than LLA and DGLA, but lower than OA and LA. It was efficiently converted into DGLA in both types of cells and increased the concentration of DGLA. LLA was converted to a small amount of C20:4 (n-3) only in Hep G2 cells. Incubation with LA, GLA, LLA, and DGLA did not increase the concentration of arachidonic acid (AA) in both types of cells. LA. GLA, LLA, and their metabolites were incorporated into phosphatidylcholine, but only GLA and its metabolite, DGLA, were also incorporated into phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. The coexistence of GLA and LLA during their catabolism diminished the amounts of respective metabolite in Hep G2 cells. The presence of GLA inhibited completely the formation of C20:4(n-3) from LLA. The results indicate that GLA is more effective in raising the ratio of DGLA/AA. Also, polyunsaturated fatty acids of n-3 and n-6 series have competitively catabolized in both types of hepatocytes.

Topics: 8,11,14-Eicosatrienoic Acid; alpha-Linolenic Acid; Animals; Carcinoma, Hepatocellular; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids; Linolenic Acids; Liver; Liver Neoplasms; Oleic Acid; Oleic Acids; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylinositols; Phosphatidylserines; Rats; Tumor Cells, Cultured

Topics: Adult; Antineoplastic Agents; Female; gamma-Linolenic Acid; Humans; Linolenic Acids; Liver Neoplasms; Male; Middle Aged

In previous communications the growth-suppressive effect of gamma-linolenic acid (GLA) dissolved in sodium carbonate in the culture media of malignant cells has been reported. In this study we show that linoleic acid (LA), the fatty acid precursor of GLA, had no growth-suppressive effect on human hepatoma cells in culture while a similar concentration of GLA suppressed malignant cell growth in culture by 69% after 10 days. This growth-suppressive effect must therefore be seen as an effect of GLA and not as a 'soap' effect. It has also been shown that the growth rate of human hepatoma cells in culture to which GLA was added daily for 5 consecutive days remained suppressed after the withdrawal of GLA from the growth medium for a further 5-day period. The striking difference between GLA and LA as regards growth suppression of human hepatoma cells in culture appears to imply a metabolic block in the hepatoma cells, involving the enzyme delta-6-desaturase, in the conversion of LA to GLA and thence via dihomo-gamma-linolenic acid to the prostaglandins of the 1 series.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Count; Cell Division; Cells, Cultured; Culture Media; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids; Linolenic Acids; Liver Neoplasms; Microscopy, Phase-Contrast

Topics: Aged; Antineoplastic Agents; Ascorbic Acid; Drug Therapy, Combination; Female; gamma-Linolenic Acid; Humans; Linolenic Acids; Liver Neoplasms; Male; Middle Aged

Topics: Aged; Antineoplastic Agents; gamma-Linolenic Acid; Humans; Linolenic Acids; Liver Neoplasms; Male; Middle Aged

Recent studies on the effects of the essential fatty acid metabolic intermediate, gamma-linolenic acid, on the growth of cancer cells in culture and on induced mammary cancer tumours in rats, strongly suggest that the metabolic defect in the cancer cells studied is simply a metabolic block involving the enzyme delta-6-desaturase. The latter enzyme is responsible for the conversion of linoleic acid to gamma-linolenic acid. These observations would suggest that cancer in the cell lines studied could be a relatively simple metabolic disease.

Topics: 8,11,14-Eicosatrienoic Acid; Alprostadil; Animals; Carcinoma, Hepatocellular; Cell Line; Cells, Cultured; Esophageal Neoplasms; Fatty Acid Desaturases; gamma-Linolenic Acid; Humans; Linolenic Acids; Liver Neoplasms; Melanoma; Metabolic Diseases; Mice; Neoplasms; Prostaglandins E; Scurvy

A further critical test of Horrobin's hypothesis that malignancy in cells may be dependent on gamma-linolenic acid (GLA) deficiency, has revealed that GLA supplementation produces a highly significant reduction in the growth rate (up to 87%) of a cultured human hepatoma cell line, compared with the growth rate of untreated hepatoma cells. This supports our previous suggestion that this hypothesis requires urgent further investigation at all levels including trials in human cancer patients.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Cells, Cultured; gamma-Linolenic Acid; Humans; Linolenic Acids; Liver Neoplasms