A new class of inhibitors of 2-arachidonoylglycerol hydrolysis and invasion of prostate cancer cells

被引：47

作者：

Nithipatikom, K

Endsley, MP

Isbell, MA

Wheelock, CE

Hammock, BD

Campbell, WB

机构：

[1] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA

[2] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA

[3] Univ Calif Davis, Canc Res Ctr, Davis, CA 95616 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2005年 / 332卷 / 04期

关键词：

2-arachidonoylglycerol; cell invasion; endocannabinoid; carboxylesterase inhibitors; prostate cancer;

D O I：

10.1016/j.bbrc.2005.05.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Endogenous 2-arachidonoylglycerol (2-AG) inhibits invasion of androgen-independent prostate cancer cells. Blocking cellular hydrolysis of 2-AG to increase its endogenous concentration results in a decrease in cell invasion. A series of compounds containing a trifluoromethyl ketone (TFK) moiety or the methyl analog (known to inhibit carboxylesterases) were investigated for their ability to inhibit 2-AG hydrolysis and prostate cancer cell invasion. Compounds containing a thioether P to a TFK moiety inhibited 2-AG hydrolysis as well as cell invasion in a concentration-dependent manner. Inhibition of 2-AG hydrolysis increased concomitantly with inhibitor alkyl chain length from 4- to 12-carbons while inhibition of cell invasion exhibited a maximum at 8- to 10-carbons of the compounds. These results demonstrate a new series of 2-AG hydrolysis inhibitors as a potential therapeutic approach for prostate cancer. (c) 2005 Elsevier Inc. All rights reserved.

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收藏

页码：1028 / 1033

页数：6

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