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

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.

• Authors: Chiara Laezza, Simona Pisanti, Elvira Crescenzi, Maurizio Bifulco
• Journal: FEBS letters (FEBS Lett) Vol. 580 Issue 26 Pg. 6076-82 (Nov 13 2006) ISSN: 0014-5793 [Print] England
• PMID: 17055492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arachidonic Acids
• Endocannabinoids
• Polyunsaturated Alkamides
• Protein Kinases
• CHEK1 protein, human
• Checkpoint Kinase 1
• CDK2 protein, human
• Cyclin-Dependent Kinase 2
• CDC25A protein, human
• cdc25 Phosphatases
• anandamide

Topics

• Arachidonic Acids (pharmacology)
• Breast Neoplasms (drug therapy)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Checkpoint Kinase 1
• Cyclin-Dependent Kinase 2 (antagonists & inhibitors)
• Endocannabinoids
• Female
• Humans
• Polyunsaturated Alkamides (pharmacology)
• Protein Kinases (drug effects)
• S Phase (drug effects)
• Tumor Cells, Cultured
• cdc25 Phosphatases (metabolism)