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

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Abstract
This study was designed to determine the molecular mechanisms underlying the anti‐proliferative effect of the endocannabinoid 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.