Polyunsaturated fatty acids (PUFAs) can influence
tumor growth and migration, both in vitro and in vivo. The PUFA
gamma-linolenic acid (GLA) has been reported to improve the poor prognosis associated with human
gliomas, although its effects at sublethal concentrations on residual cells postsurgery are poorly understood. The study investigated the effects sublethal PUFA doses (90 or 150 microM) may have on rat C6
glioma cell energy metabolism, since an adequate energy supply is essential for cell proliferation, migration, and apoptosis. Of note was the identification of mitochondrial heterogeneity in relation to the mitochondrial membrane potential (
MMP), which has been suggested but unproven in previous studies. GLA and
eicosapentaenoic acid (EPA) caused significant changes in cellular
fatty acid composition and increased the percentage of cells with a low
MMP after a 96-h exposure period. The presence of PUFAs inhibited C6 cell proliferation and migration, although apoptosis was not induced. The
protein expression and activity of
glucose-6-phosphate dehydrogenase was increased after 96-h incubation with 90 microM GLA and EPA and would allow redox regulation through increased
NADPH production, permitting the maintenance of adequate intracellular
reduced glutathione concentrations and limiting rates of lipid peroxidation and
reactive oxygen species generation. Neither
NADP(+)-isocitrate dehydrogenase nor
NADP(+)-malate dehydrogenase activity responded to PUFAs, suggesting it is
glucose-6-phosphate dehydrogenase that is the principal source of
NADPH in C6 cells. These data compliment studies showing that higher concentrations of GLA induced
glioma cell death and
tumor regression and suggest that GLA treatment could be useful for the inhibition of residual cell proliferation and migration after surgical removal of the
tumor mass.