Palmitoylethanolamide And Human Breast Cancer Cells

[Julie Gardener]

Palmitoylethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the anti-proliferative effect of anandamide in human breast cancer cell​

Vincenzo DI MARZO, Dominique MELCK, Pierangelo ORLANDO"¹, Tiziana
BISOGNO, Orna ZAGOORYÅ’, Maurizio BIFULCO, Zvi VOGELÅ’ and Luciano DE PETROCELLI
Biochem. J. (2001)

Abstract

Palmitoylethanolamide (PEA) has been shown to act in synergy with anandamide (arachidonoylethanolamide; AEA), an en-dogenous agonist of cannabinoid receptor type 1 (CB"). This synergistic effect was reduced by the CB # cannabinoid receptor antagonist SR144528, although PEA does not activate either CB" or CB# receptors. Here we show that PEA potently enhances the anti-proliferative effects of AEA on human breast cancer cells (HBCCs), in part by inhibiting the expression of fatty acid amide hydrolase (FAAH), the major enzyme catalysing AEA degradation. PEA (1±10 lM) enhanced in a dose-related manner the inhibitory effect of AEA on both basal and nerve growth factor (NGF)-induced HBCC proliferation, without inducing any cytostatic effect by itself. PEA (5 lM) decreased the IC &! values for AEA inhibitory effects by 3±6-fold. This effect was not blocked by the CB #
receptor antagonist SR144528, and was not mimicked by a selective agonist of CB # receptors. PEA enhanced AEA-evoked inhibition of the expression of NGF Trreceptors, which underlies the anti-proliferative effect of the endocannabinoid on NGF-stimulated MCF-7 cells. The effect of PEA was due in part to inhibition of AEA degradation, since treatment of MCF-7 cells with 5 lM PEA caused a C30±40% down-regulation of FAAH expression and activity. However, PEA also enhanced the cytostatic effect of the cannabinoid receptor agonist HU-210, although less potently than with AEA. PEA did not modify the affinity of ligands for CB" or CB# receptors, and neither did it alter the CB" }CB #-mediated inhi-bitory effect of AEA on adenylate cyclase type V, nor the expression of CB" and CB# receptors in MCF-7 cells. We suggest that long-term PEA treatment of cells may positively affect the pharmacological activity of AEA, in part by inhibiting FAAH expression.

Source: Palmitoylethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the anti-proliferative effect of anandamide in human breast cancer cell