Arch Toxicol  2003 Apr;77(4):201-7 

AM404 and VDM 11 non-specifically inhibit C6 glioma cell proliferation at
concentrations used to block the cellular accumulation of the endocannabinoid
anandamide.

Jonsson KO, Andersson A, Jacobsson SO, Vandevoorde S, Lambert DM, Fowler CJ.

Department of Pharmacology and Clinical Neuroscience, Umea University, 901 87,
Umea, Sweden, kentolov.jonsson@pharm.umu.se

AM404 [ N-(4-hydroxyphenyl)arachidonylamide] and VDM 11 [(5 Z,8 Z,11 Z,14 Z)-
N-(4-hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide] are commonly used to
prevent the cellular accumulation of the endocannabinoid anandamide, and thereby
to potentiate its actions. However, it has been reported that AM404 can produce
an influx of calcium into cells, which might be expected to have deleterious
effects on cell proliferation. In the present study, AM404 and VDM 11 were found
to reduce C6 glioma cell proliferation with IC(50) values of 4.9 and 2.7 micro
M, respectively. The inhibition of cell proliferation following a 96-h exposure
was not accompanied by dramatic caspase activation, and was not prevented by
either a combination of cannabinoid and vanilloid receptor antagonists, or by
the antioxidant alpha-tocopherol, suggestive of a non-specific mode of action.
Similar results were seen with palmitoylisopropylamide, although this compound
only produced significant inhibition of cell proliferation at 30 micro M
concentrations. AM404 (1 micro M), VDM 11 (1 micro M) and
palmitoylisopropylamide (3-30 micro M), i.e. concentrations producing relatively
modest effects on cell proliferation per se, reduced the vanilloid
receptor-mediated antiproliferative effects of anandamide, as would be expected
for compounds preventing the cellular accumulation of anandamide (and thereby
access to its binding site on the vanilloid receptor). It is concluded that
concentrations of AM404 and VDM 11 that are generally used to reduce the
cellular accumulation of anandamide have deleterious effects upon cell
proliferation, and that lower concentrations of these compounds may be more
appropriate to use in vitro.

PMID: 12698235 [PubMed - in process]