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
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.
引用
收藏
页码:1028 / 1033
页数:6
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