一类新型的2-花生四烯酸甘油水解抑制剂及前列腺癌细胞侵袭抑制剂。
A new class of inhibitors of 2-arachidonoylglycerol hydrolysis and invasion of prostate cancer cells.
作者信息
Nithipatikom Kasem, Endsley Michael P, Isbell Marilyn A, Wheelock Craig E, Hammock Bruce D, Campbell William B
机构信息
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
出版信息
Biochem Biophys Res Commun. 2005 Jul 15;332(4):1028-33. doi: 10.1016/j.bbrc.2005.05.049.
Abstract
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 beta 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.
摘要
内源性2-花生四烯酸甘油酯（2-AG）可抑制雄激素非依赖性前列腺癌细胞的侵袭。阻断细胞对2-AG的水解以增加其内源性浓度会导致细胞侵袭减少。研究了一系列含有三氟甲基酮（TFK）部分或甲基类似物（已知可抑制羧酸酯酶）的化合物抑制2-AG水解和前列腺癌细胞侵袭的能力。TFK部分β位含有硫醚的化合物以浓度依赖性方式抑制2-AG水解以及细胞侵袭。随着抑制剂烷基链长度从4个碳增加到12个碳，2-AG水解的抑制作用随之增加，而细胞侵袭的抑制作用在化合物的8至10个碳时表现出最大值。这些结果证明了一系列新型的2-AG水解抑制剂可作为前列腺癌的一种潜在治疗方法。
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本文引用的文献
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