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Anandamide inhibits Cdk2 and activates Chk1 leading to cell cycle arrest in human breast cancer cells
Author(s) -
Laezza Chiara,
Pisanti Simona,
Crescenzi Elvira,
Bifulco Maurizio
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.09.074
Subject(s) - anandamide , endocannabinoid system , cell cycle checkpoint , cdc25a , chemistry , cell cycle , microbiology and biotechnology , cell growth , cancer research , blockade , cancer cell , cancer , pharmacology , cannabinoid receptor , cell , biology , receptor , medicine , biochemistry , agonist
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.