Anandamide inhibits Cdk2 and activates Chk1 leading to cell cycle arrest in human breast cancer cells |
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Authors: | Laezza Chiara Pisanti Simona Crescenzi Elvira Bifulco Maurizio |
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Affiliation: | IEOS CNR, Napoli, Italy. chilaez@hotmail.com |
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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. |
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Keywords: | CB1, cannabinoid receptor 1 CB2, cannabinoid receptor 2 Met-F-AEA, 2-methyl-arachidonoyl-2′-F-ethylamide Rb, retinoblastoma Cdk, cyclin dependent kinase CKIs, cdk inhibitors HU, hydroxyurea |
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