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Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2007 Dec 07; Vol. 364 (1), pp. 131-7. Date of Electronic Publication: 2007 Oct 02. - Publication Year :
- 2007
-
Abstract
- Time-lapse microscopy of human lung cancer (H460) cells showed that the endogenous cannabinoid anandamide (AEA), the phyto-cannabinoid Delta-9-tetrahydrocannabinol (THC) and a synthetic cannabinoid HU 210 all caused morphological changes characteristic of apoptosis. Janus green assays of H460 cell viability showed that AEA and THC caused significant increases in OD 595 nm at lower concentrations (10-50 microM) and significant decreases at 100 microM, whilst HU 210 caused significant decreases at all concentrations. In rat heart mitochondria, all three ligands caused significant decreases in oxygen consumption and mitochondrial membrane potential. THC and HU 210 caused significant increases in mitochondrial hydrogen peroxide production, whereas AEA was without significant effect. All three ligands induced biphasic changes in either mitochondrial complex I activity and/or mitochondrial complex II-III activity. These data demonstrate that AEA, THC, and HU 210 are all able to cause changes in integrated mitochondrial function, directly, in the absence of cannabinoid receptors.
- Subjects :
- Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Electron Transport Complex I drug effects
Electron Transport Complex II drug effects
Electron Transport Complex III drug effects
Endocannabinoids
Humans
Hydrogen Peroxide metabolism
Lung Neoplasms
Membrane Potential, Mitochondrial drug effects
Models, Biological
Oxygen Consumption drug effects
Apoptosis drug effects
Arachidonic Acids pharmacology
Cannabinoid Receptor Agonists
Cannabinoids pharmacology
Dronabinol analogs & derivatives
Dronabinol pharmacology
Mitochondria drug effects
Mitochondria physiology
Polyunsaturated Alkamides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 364
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 17931597
- Full Text :
- https://doi.org/10.1016/j.bbrc.2007.09.107