Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non‐tumour brain tissue
- 2 March 2005
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 93 (2), 299-309
- https://doi.org/10.1111/j.1471-4159.2005.03013.x
Abstract
The endogenous levels of the two cannabinoid receptor ligands 2-arachidonoyl glycerol and anandamide, and their respective congeners, monoacyl glycerols and N-acylethanolamines, as well as the phospholipid precursors of N-acylethanolamines, were measured by gas chromatography-mass spectrometry in glioblastoma (WHO grade IV) tissue and meningioma (WHO grade I) tissue and compared with human non-tumour brain tissue. Furthermore, the metabolic turnover of N-acylethanolamines was compared by measurements of the enzymatic activity of N-acyltransferase, N-acylphosphatidylethanolamine-hydrolysing phospholipase D and fatty acid amide hydrolase in the same three types of tissue. Glioblastomas were characterized by enhanced levels of N-acylethanolamines (eightfold, 128 +/- 59 pmol/micromol lipid phosphorus) including anandamide (17-fold, 4.6 +/- 3.1 pmol/micromol lipid phosphorus) and several species of N-acylphosphatidylethanolamines (three to eightfold). This was accompanied by a more than 60% reduction in the enzyme activities of N-acylphosphatidylethanolamine-hydrolysing phospholipase D and fatty acid amide hydrolase. By contrast, meningiomas were characterized by a massively enhanced level of 2-monoacyl glycerols (20-fold, 2293 +/- 361 pmol/micromol lipid phosphorus) including 2-arachidonoyl glycerol (20-fold, 1524 +/- 361 pmol/micromol lipid phosphorus). This was accompanied by an enhanced in vitro conversion of phosphatidylcholine to monoacyl glycerol (fivefold). The enhanced level of the 2-arachidonoyl glycerol, anandamide and other N-acylethanolamines detected in the two types of tumour tissue may possibly act as endogenous anti-tumour mediators by stimulation of both cannabinoid and non-cannabinoid receptor-mediated mechanisms.Keywords
This publication has 70 references indexed in Scilit:
- Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in GliomasCancer Research, 2004
- Molecular approaches to brain tumour invasionActa Neurochirurgica, 2003
- Ceramide levels are inversely associated with malignant progression of human glial tumorsGlia, 2002
- Anandamide, but not 2‐arachidonoylglycerol, accumulates during in vivo neurodegenerationJournal of Neurochemistry, 2001
- Δ9‐Tetrahydrocannabinol induces apoptosis in C6 glioma cellsFEBS Letters, 1998
- Potential Biosynthetic Connections between the Two Cannabimimetic Eicosanoids, Anandamide and 2-Arachidonoyl-Glycerol, in Mouse Neuroblastoma CellsBiochemical and Biophysical Research Communications, 1996
- Arachidonoyl ethanolamide-[1,2-14C] as a substrate for anandamide amidaseLife Sciences, 1995
- Phospholipid content and composition of human meningiomasNeurochemical Pathology, 1984
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976
- Isolation, Structure, and Partial Synthesis of an Active Constituent of HashishJournal of the American Chemical Society, 1964