HEP (2005) 168:627–642
©cSpringer-Verlag 2005
Effects on Cell Viability
M. Guzmán
Department of Biochemistry and Molecular Biology I, School of Biology,
Complutense University, 28040 Madrid, Spain
[email protected]
1 Cannabinoid Signalling Pathways and Cell Viability .............. 628
2TumourCells.................................... 629
2.1 AntitumouralEffect................................ 629
2.2 MechanismofAction ............................... 630
2.2.1Apoptosis ..................................... 630
2.2.2CellGrowthArrest................................. 631
2.2.3InhibitionofAngiogenesis ............................ 631
3NeuralCells.................................... 632
3.1 NeuroprotectiveEffect............................... 632
3.1.1MechanismofAction ............................... 633
3.2 NeurotoxicEffect ................................. 634
3.2.1MechanismofAction ............................... 634
3.3 GlioprotectiveEffect................................ 634
3.3.1MechanismofAction ............................... 635
4ImmuneCells................................... 635
4.1 CellDeath/SurvivalEffect............................. 635
4.2 MechanismofAction ............................... 636
5 Potential Therapeutic Implications ....................... 637
References ........................................ 638
AbstractCannabinoids are known to control the cell survival/death decision,
leading to different outcomes that depend on the nature of the target cell and
its proliferative or differentiation status. Cannabinoids induce growth arrest or
apoptosis in a number of transformed cells in culture. They do so by modulating
key cell signalling pathways involved in the control of tumour cell fate. The best-
characterised example is cannabinoid-induced apoptosis of glioma cells, which
occurs via sustained ceramide accumulation, extracellular signal-regulated kinase
activation and Akt inhibition. In addition, cannabinoid administration inhibits the
angiogenesis and slows the growth of different types of tumours in laboratory an-
imals. By contrast, most of the experimental evidence indicates that cannabinoids
protect normal neurons and glial cells from apoptosis as induced by toxic insults
such as glutamatergic overstimulation, ischaemia and oxidative damage. It is there-
fore very likely that cannabinoids regulate cell survival and cell death pathways