γ-Linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to 'normal' rat astrocytes

Abstract

Summary This study compares the effect of y-linolenic acid (GLA) and its precursor linoleic acid (LA) on survival of 36B10 malignant rat astrocytoma cells and 'normal' rat astrocytes. GLA was cytotoxic to 36B10 cells but not to astrocytes. By contrast, LA supplementation did not affect the survival of either cell types. There were minor differences in the uptake, distribution and use of radiolabelled GLA and LA by the 36B1 0 cells and astrocytes. GLA and LA supplementation increased the total polyunsaturated fatty acid (PUFA) content of the cells indicating increased oxidative potential. However, elevated levels of 8-isoprostane, an indicator of increased oxidative stress, were only observed in the GLA supplemented 36B10 cells. Addition of the antioxidant trolox to GLA-enriched 36B10 cells blocked the cytotoxic effect. Further, GLA enhanced the radiation sensitivity of the astrocytoma cells but not the astrocytes; trolox blocked the GLA-mediated increase in astrocytoma cell radiosensitivity. LA did not affect the radiation response of either cell type. While cyclo-oxygenase inhibitors did not affect GLA cytotoxicity, they blocked the enhanced radiation response of GLA-supplemented cells. The lipoxygenase inhibitor NDGA did not affect the toxicity produced by GLA. Thus, GLA is toxic to the neoplastic astrocytoma cells but not to normal astrocytes.Keywords: polyunsaturated fatty acids; y-linolenic acid; linoleic acid; astrocytoma; astrocyte; radiation Gamma linolenic acid (GLA, 18:3n6) supplementation has been reported to suppress the growth of tumour cells in vitro (Fujiwara et al, 1986;Sangeetha and Das, 1992;Falconer et al, 1994) and in vivo (Karmali et al, 1985;Abou et al, 1987). Interestingly, in separate studies conducted on normal tissues in vivo, it has been reported that dietary GLA decreases the severity of radiation damage to the skin (Hopewell et al, 1993) and CNS (Hopewell et al, 1994). We have previously shown that GLA supplementation can decrease clonogenic cell survival of malignant rat astrocytoma cells and increase their radiosensitivity (Vartak et al, 1997). To determine the therapeutic potential of this observation, it is important to investigate the effect of GLA on 'normal' rat astrocytes. The purpose of this work was to compare the effects of GLA on the survival of 36B10 astrocytoma cells and astrocytes and their response to radiation. The uptake and use of GLA by astrocytoma cells has also been compared with that by astrocytes.The cytotoxic action of polyunsaturated fatty acids (PUFAs) is thought to be mediated predominantly via lipid peroxidation and free radical generation (Begin et al, 1988;Ells et al, 1996). Several studies also indicate that eicosanoid and leukotriene synthesis play an important role in tumour cell proliferation and metastasis (Earashi et al, 1995; Damtew and Spagnuolo, 1997). Arachidonic acid (AA, 20:4n6) and dihomo-y-linolenic acid (DGLA, 20:3n6) are the substrate for the biosynthesis of prostaglandins of the 2-and 1-series respectively (Crawford, 1983 Bell JG et ...

Docosahexaenoic acid enhances arsenic trioxide–mediated apoptosis in arsenic trioxide–resistant HL-60 cells

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Fatty acid synthase: a novel target for antiglioma therapy

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A nucleotide insertion in the transcriptional regulatory region of FADS2 gives rise to human fatty acid delta-6-desaturase deficiency

“…The mouse embryo fibroblasts were maintained in DMEM containing 10% FBS, 4 mM l -glutamine, 50 g/ml gentamycin, and 4.5 g/l glucose. Cell viability was determined using the commercially available calcein AM reagent obtained from Molecular Probes (Eugene, OR) according to the specifications of the supplier (13,14).…”

“…This patient developed clinical symptoms characteristic of essential fatty acid deficiency shortly after birth, and GLC analysis of her plasma fatty acid composition indicated low levels of both arachidonic acid and DHA. We demonstrated that cultured skin fibroblasts obtained from this patient converted 85% to 95% less [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]linoleic acid to arachidonic acid than corresponding normal fibroblast cultures (5). Our results also indicated that the conversion of radiolabeled PUFA precursors to DHA was markedly reduced in the patient's fibroblasts.…”