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Antitumour
and pro-apoptotic actions of highly unsaturated fatty acids in glioma
Leaver
HA, Bell HS, Rizzo MT, Ironside JW, Gregor A, Wharton SB, Whittle IR
Department
of Clinical Neurosciences, Edinburgh University, UK
The
highly unsaturated fatty acids (HUFA) of the n-6 and n-3 series are involved in
cell signalling in normal and transformed cells and have recently been
associated with pathways leading to tumour cell death.
The antitumour activity of three HUFA (arachidonic acid, gamma linolenic acid
and eicosapentaenoic acid) were studied in glioma cells and tissue.
Using five glioma models, including primary cell suspensions prepared from 46
human glioma samples and an in vivo rat C6 glioma model, we obtained evidence
that, following exposure to HUFA, either administered into the medium
surrounding human glioma cells or in 16 preparations of multicellular spheroids
derived from human and rodent glioma cell lines (C6, MOG, U87, U373) or
administered intra-tumourally by infusion using osmotic mini-pumps in 48 rats,
glioma regression and apoptosis were detected.
Additionally, synergy between gamma irradiation and HUFA administration was
observed in 13 experiments analyzing C6 glioma cell apoptosis in vitro.
These pro-apoptotic and antiproliferative 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 neural tissue and
vasculature in adjacent brain was observed.
Also, there was little evidence of acute inflammatory infiltration in regressing
tumours.
Our findings suggest that intraparenchymal infusion of HUFA may be effective in
stimulating glioma regression.
Copyright 2002 Elsevier Science Ltd. All rights reserved.
PMID: 12051954 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12051954&dopt=Abstract
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