Anandamide inhibits Cdk2 and activates Chk1 leading to cell cycle arrest in human breast cancer cells
Anandamide inhibits Cdk2 and activates Chk1 leading to cell cycle arrest in human breast cancer cells
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DOI：
10.1016/j.febslet.2006.09.074
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发表时间：
2006-11-13
期刊：
影响因子：
3.5
通讯作者：
Bifulco, Maurizio
中科院分区：
文献类型：
--
作者：
Laezza, Chlara;Pisanti, Simona;Bifulco, Maurizio
这项研究旨在确定内源性大麻素anandamide对高度侵袭性人乳腺癌细胞MDA-MB-231的抗增殖作用的分子机制。我们发现，代谢稳定的anandamide类似物，Met-F-AEA，诱导与Chk 1激活，Cdc 25 A降解和Cdk 2活性抑制相关的S期生长停滞。这些发现表明，Met-F-AEA诱导的细胞周期阻滞依赖于关键S期调节蛋白的表达和活性的调节。观察到的作用机制，已经报道了众所周知的化疗药物，提供了强有力的证据，在细胞周期检查点的激活的花生四烯酸相关化合物的直接作用。(c)2006年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
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.