gamma-linolenic-acid and Melanoma

Maspin, mammary serine protease inhibitor, is a recently identified tumour suppressor and has a profound effect on cell motility. This study examined the effect of gamma linolenic acid (GLA), an essential fatty acid (EFA) with anticancer properties, on the expression of maspin and motility of cancer cells. Six human cell lines including colon cancer, mammary cancer, and melanoma were used. Expression of maspin protein was determined by immunocytochemistry & Western blotting. Maspin mRNA was detected with reverse transcription-PCR (RT-PCR). Four of the six cell types expressed maspin with MDA MB 231 and ECV304 (endothelial cell) being negative. Treatment of these maspin positive cells with gamma linolenic acid (GLA) resulted in a concentration dependent stimulation of the expression of maspin protein with the effects seen as early as 4 hours. Linoleic acid had an inhibitory effects. Alpha linolenic acid and arachidonic acid had no significant effect. The mRNA levels from cells treated with GLA was seen to increase as shown by RT-PCR. Cell motility, monitored with time-lapse video recording and Hoffmann microscopy, showed a marked reduction in terms of spreading and migration on extracellular matrix coated surface. This reduction was reversed with anti-maspin antibody. It is concluded that GLA, a member of then-6 series of EFAs, up-regulates the expression of maspin which is associated with a reduction in the motility of cancer cells.

Topics: Breast Neoplasms; Cell Line; Cell Movement; Colonic Neoplasms; Endothelium, Vascular; Fatty Acids, Nonesterified; Female; gamma-Linolenic Acid; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Kinetics; Melanoma; Polymerase Chain Reaction; Protein Biosynthesis; Proteins; RNA, Messenger; Serine Proteinase Inhibitors; Serpins; Transcription, Genetic; Tumor Cells, Cultured

This study examined the effects of linoleic acid (LA) and gamma-linolenic acid (GLA) on BL6 melanoma growth in cell culture and of safflower oil (SFO) which contains LA and evening primrose oil (EPO) which contains GLA, on melanoma growth when grown in mice. The delta-6-desaturase activity of the melanoma cells in the two systems was also examined and an attempt made to relate the activity of the enzyme to the effects of GLA on cell and tumour growth. LA and GLA were found to be equipotent in inhibiting growth of the in vitro cultured BL6 cells which were found to contain an appreciable level of delta-6-desaturase activity. EPO was however found to be a more potent promoter of in vivo melanoma growth in mice than SFO. Melanomas grown in mice were found to lack delta-6-desaturase activity suggesting that the EPO diet, by providing GLA, was able to compensate for the loss of enzyme activity in the melanomas. The possibility that melanomas in mice have a requirement for GLA for growth while in in vitro cultured cells excess GLA inhibits the growth of the cells through an increase in lipid peroxidation is discussed.

Topics: Animals; Antineoplastic Agents; Cell Transformation, Neoplastic; Fatty Acid Desaturases; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Linoleic Acids; Linolenic Acids; Linoleoyl-CoA Desaturase; Lipid Peroxidation; Melanoma; Mice; Mice, Inbred C57BL; Microsomes, Liver; Oenothera biennis; Plant Oils; Safflower Oil; Tumor Cells, Cultured

Topics: Antineoplastic Agents; Blood Viscosity; Fatty Acids, Essential; Fish Oils; gamma-Linolenic Acid; Humans; Linoleic Acids; Melanoma; Oenothera biennis; Plant Oils

Topics: Dietary Fats, Unsaturated; Fatty Acids, Essential; gamma-Linolenic Acid; Hypolipidemic Agents; Linoleic Acids; Melanoma; Oenothera biennis; Plant Oils; Skin Neoplasms

Topics: Antineoplastic Agents; Fats, Unsaturated; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linoleic Acids; Melanoma; Oenothera biennis; Plant Oils; Skin Neoplasms

Topics: Antineoplastic Agents; Dietary Fats, Unsaturated; gamma-Linolenic Acid; Humans; Linolenic Acids; Melanoma; Skin Neoplasms

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