gamma-linolenic-acid and Neuroblastoma

We examined the effect of gamma-linolenic acid (GLA) supplementation on the growth and fatty acid composition of three human tumor cell lines (the neuroblastoma CHP-212, the tubal carcinoma TG, and the colon carcinoma SW-620), in order to evaluate the relationship between GLA-induced tumor cell death and the distribution of fatty acids in tumor cells. At the highest GLA concentrations (10 and 20 micrograms/ml), the DNA synthesis was completely abolished; at 5 micrograms/ml GLA only SW-620 cells did not proliferate, while CHP-212 and TG cells showed a residual [3H]-thymidine incorporation. GLA levels were very low in cells grown in control medium; GLA supplementation caused a significant incorporation of GLA itself in all the cell lines at each concentration. In TG and CHP-212 cells, GLA was metabolized, although to a different extent, to dihomo-gamma linolenic acid and arachidonic acid. SW-620 cells neither elongated nor desaturated the incorporated GLA. The highest cytostatic effect was reached when GLA was not transformed into its metabolites, suggesting that the GLA toxicity to tumor cells is not dependent on metabolites but is due to GLA itself.

Topics: Cell Division; Colonic Neoplasms; Fallopian Tube Neoplasms; Fatty Acids; Female; gamma-Linolenic Acid; Humans; Neuroblastoma; Tumor Cells, Cultured

Two human neuroblastoma cell lines, NCG and GOTO, were used to study the cytotoxic effect of gamma linolenic acid (GLA). The cell growth inhibition of these culture cells by GLA was found to be associated with striking membrane fatty acid modification. When culture cells were exposed to 20 micrograms/ml and 60 micrograms/ml GLA for 48 hr, polyenoic acids in cell membrane phospholipids (PC, PE, PI, PS) and triglyceride significantly increased; 1.8-21.0 fold for NCG and 1.04-11.5 fold for GOTO, in association with decreased monoenoic acids. The most remarkable changes were; increase of C18:3, C20:3, C20:4 and decrease of C18:1. CoQ10 (50 micrograms/ml) and vitamin E (10 microM) shown to protect against the cytotoxic effect of GLA did not modify the incorporation of GLA into tumor cells. These results indicate that the antitumor effect of GLA is probably due to cellular dysfunction caused by fatty acid modification after GLA incorporation.

Topics: Antineoplastic Agents; Cell Division; Cell Membrane; Fatty Acids; gamma-Linolenic Acid; Humans; Linolenic Acids; Membrane Lipids; Neuroblastoma; Tumor Cells, Cultured; Ubiquinone; Vitamin E

gamma-linolenic acid (GLA) was found to suppress the cell growth of 4 human neuroblastoma cell lines. GOTO was the most sensitive, followed by SK-N-DZ and NKP, while NCG was much less sensitive to GLA. In terms of GLA cytotoxicity, neither cyclo-oxygenase inhibitors nor a lipoxygenase inhibitor showed any effect. On the other hand, 4 antioxidants (Coenzyme Q, (D) alpha-tocopherol, (DL) alpha-tocopherol, butylated hydroxytoluene) reduced the growth inhibitory effect of GLA, but not in proportion to the decrease of GLA-stimulated lipid peroxidation. Accordingly, prostaglandins and leukotrienes probably do not play a role, and lipid peroxide may only be partly involved in the GLA effect.

Topics: Antineoplastic Agents; Antioxidants; Cell Line; Cyclooxygenase Inhibitors; gamma-Linolenic Acid; Humans; Linolenic Acids; Lipid Peroxides; Lipoxygenase Inhibitors; Neuroblastoma; Ubiquinone