Anandamide inhibits Cdk2 and activates Chk1 leading to cell cycle arrest in human breast cancer cells

This study was designed to determine the molecular mechanisms underlying the anti-proliferative effect of the endo-cannabinoid anandamide on highly invasive human breast cancer cells, MDA-MB-231. We show that a metabolically stable analogue of anandamide, Met-F-AEA, induces an S phase growth arrest correlated with Chk1 activation, Cdc25A degradation and suppression of Cdk2 activity. These findings demonstrate that Met-F-AEA induced cell cycle blockade relies on modulated expression and activity of key S phase regulatory proteins. The observed mechanism of action, already reported for well-known chemotherapeutic drugs, provides strong evidence for a direct role of anandamide related compounds in the activation of cell cycle checkpoints. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.