gamma-linolenic-acid and Carcinoma--Hepatocellular

gamma-Linolenic acid (GLA) is known to have selective tumoricidal action. In this study, the effect of lithium salt of GLA conjugated to iodized lymphographic oil (LGIOC) was injected intra-arterially close to the origin of tumor-feeding vessel(s) was studied. Four patients with stage 4 cancer disease (2 with hepatocellular carcinoma, 1 with giant cell tumor of the bone, and one with renal cell carcinoma), were selected for the study. Angiography, radiography and computed axial tomography were performed prior to and immediately after the injection of LGIOC and at periodic intervals. All four patients tolerated the treatment well. The most significant observation was the complete occlusion of the tumor-feeding vessels after LGIOC injection. Follow-up angiograms performed in all the patients showed occlusion of the tumor-feeding vessels is more or less permanent. A significant reduction in the size of the tumor was also observed in these patients. LGIOC showed occlusion of tumor-feeding vessels after infusion, and further studies are needed to confirm these preliminary results.

Topics: Adult; Aged; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; gamma-Linolenic Acid; Giant Cell Tumor of Bone; Humans; Male; Middle Aged; Neoplasms; Radiography

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

Hepatocellular carcinoma (HCC) is one of the known major health problems across the globe, and is sixth ranked among all cancer, due to its high mortality rate. Polyunsaturated fatty acids (PUFAs) play an important role in the formation of a cell membrane, along with the fluidity of the membrane and proteins. Gamma linolenic acid (GLA) is member of the ω-6 family of PUFAs and converts into the arachidonic acid via a series of elongation and desaturation reactions. The aim of the current investigation was to scrutinize the effect of GLA on mitochondrial mediated apoptosis and anti-inflammatory pathway against diethylnitrosamine (DEN) induced HCC.. Chemical carcinogenesis in Wistar rats was introduced by an intra-peritoneal dose of DEN (200 mg/kg). The rats received the various doses of GLA for 22 weeks. The progressions of serum biomarkers and histopathology components of hepatic tissue were used to access the prophylactic effects. The antioxidant parameters, cancer preventive agent status, and apoptosis mechanism were reviewed to scrutinize the possible mechanism.. Dose-dependent treatment of GLA significantly (. On the basis of the above results, we can conclude that the GLA exhibited a chemo-protective effect against DEN induced HCC that might be due to the altered hypoxic microenvironment, mitochondrial mediated death apoptosis, and anti-inflammatory pathway, respectively.

Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Apoptosis; Apoptosis Regulatory Proteins; Carcinoma, Hepatocellular; Diethylnitrosamine; Female; gamma-Linolenic Acid; Hypoxia-Inducible Factor-Proline Dioxygenases; Liver Neoplasms, Experimental; Male; Mitochondria; Procollagen-Proline Dioxygenase; Rats, Wistar; Signal Transduction; Tumor Hypoxia; Tumor Microenvironment

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

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

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