Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Anti-tumour actions of highly unsaturated fatty acids in glioma models

HA Leaver, HS Bell, JW Ironside, A Gregor, SB Wharton, IR Whittle

Clinical Neurosciences, Oncology & Neuropathology, University of Edinburgh, UK,

AIM: The highly unsaturated fatty acids (HUFA) of the n-6 and n-3 series are involved in cell signaling in normal and transformed cells and in pathways leading to tumour cell death. The anti-tumour activity of three HUFA (arachidonic acid, gamma linolenic acid and eicosapentaenoic acid) were studied in glioma cells and tissue. METHODS & RESULTS: Using five glioma models, including primary cell suspensions prepared from human glioma samples and an in vivo rat C6 glioma infusion model, we obtained evidence that following exposure to HIUFA of the n-6 and n-3 series, either administered into the medium containing human glioma cells or multicellular spheroids derived from human and rodent glioma cell lines (mog, al72, U87, U373) or administered intra-tumorally by infusion using osmotic mini-pumps in 48 rats, glioma regression and apoptosis were detected, using five assays of apoptosis. Additionally, synergy between gamma irradiation and HUFA administration was observed in C6 g! glioma cell apoptosis and oxidative metabolism. These activities were observed using both C18 and C20 fatty acids of the n-6 and n-3 series, but not when saturated and monounsaturated C18 and C20 fatty acid preparations were used. In the glioma infusion model, in addition to the apoptosis detected in glioma tissue infused with HUFA for 3-7 days, preservation of normal neuronal tissue and vasculature in adjacent brain was observed. Also, there was little evidence of acute inflammatory infiltration in regressing tumors. CONCLUSION: Our findings suggest that intraparechymal infusion of HUFA may be effective in stimulating glioma regression.

KEY WORDS: cell signaling, highly unsaturated fatty acids (HUFA), glioma regression.

For more information, contact

Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on satellite symposium.