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  • Increasing antiproliferative properties of endocannabinoids in N1E-115 neuroblastoma cells through inhibition of their metabolism.

Increasing antiproliferative properties of endocannabinoids in N1E-115 neuroblastoma cells through inhibition of their metabolism.

PloS one (2011-11-03)
Laurie Hamtiaux, Laurie Hansoulle, Nicolas Dauguet, Giulio G Muccioli, Bernard Gallez, Didier M Lambert
RESUMEN

The antitumoral properties of endocannabinoids received a particular attention these last few years. Indeed, these endogenous molecules have been reported to exert cytostatic, apoptotic and antiangiogenic effects in different tumor cell lines and tumor xenografts. Therefore, we investigated the cytotoxicity of three N-acylethanolamines--N-arachidonoylethanolamine (anandamide, AEA), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA)--which were all able to time- and dose-dependently reduce the viability of murine N1E-115 neuroblastoma cells. Moreover, several inhibitors of FAAH and NAAA, whose presence was confirmed by RT-PCR in the cell line, induced cell cytotoxicity and favored the decrease in cell viability caused by N-acylethanolamines. The most cytotoxic treatment was achieved by the co-incubation of AEA with the selective FAAH inhibitor URB597, which drastically reduced cell viability partly by inhibiting AEA hydrolysis and consequently increasing AEA levels. This combination of molecules synergistically decreased cell proliferation without inducing cell apoptosis or necrosis. We found that these effects are independent of cannabinoid, TRPV1, PPARα, PPARγ or GPR55 receptors activation but seem to occur through a lipid raft-dependent mechanism. These findings further highlight the interest of targeting the endocannabinoid system to treat cancer. More particularly, this emphasizes the great potential benefit of designing novel anti-cancerous therapies based on the association of endocannabinoids and inhibitors of their hydrolysis.

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Sigma-Aldrich
Methyl-β-cyclodextrin, produced by Wacker Chemie AG, Burghausen, Germany, ≥95.0% cyclodextrin basis (calculated)
Sigma-Aldrich
Methyl-β-cyclodextrin, Produced by Wacker Chemie AG, Burghausen, Germany, Life Science, ≥98.0% cyclodextrin basis
Sigma-Aldrich
Methyl-β-cyclodextrin, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Methyl-β-cyclodextrin, average Mn 1310
Sigma-Aldrich
Methyl-β-cyclodextrin
Sigma-Aldrich
N-Oleoylethanolamine, ~98% (TLC)
Sigma-Aldrich
GW6471, ≥98% (HPLC)