来源：生物谷 2013-09-26 21:27
2013年9月27日讯 /生物谷BIOON/--近日发表在Biochemical Pharmacology杂志上的文章称，科学家揭示了抗炎症药物布洛芬阻止某些癌症进一步发展的机制。
布洛芬是药物家族NSAIDs的成员之一，与扑热息痛和阿司匹林一样都是最常见的非处方药。有证据称长期服用布洛芬能够更好对抗前列腺癌，部分结肠癌和其他类型癌症。
不像其他药物，布洛芬有两种存在形式，R型和S型。仅S型具有抗炎症效果，而R型是非活性形式。而机体可以通过手型对称转换的方式将R-布洛芬转化为S-布洛芬。而该转化的连带好处就是具有抗癌效果。
由于手型对称转换关键酶alpha-methylacyl-CoA racemase (AMACR)在前列腺癌，部分结肠癌和其他类型癌症中的表达水平上调。科学家推测布洛芬在机体中的转化事实上是降低了该酶的正常活性，进一步阻断癌症的进一步发展。
该研究的通讯作者Lloyd博士称，布洛芬在人体中的手型转换在1970年就已经被发现，然而直到现在才了解该转换不同过程需要的蛋白质。
Lloyd博士补充道，我们重点研究了手型转换最后的一个酶在抗癌过程中的作用，这将有助于我们理解布洛芬抗击癌症的机制。（生物谷Bioon.com）
Hydrolysis of ibuprofenoyl-CoA and other 2-APA-CoA esters by human acyl-CoA thioesterases-1 and -2 and their possible role in the chiral inversion of profens
Qu X, Allan A, Chui G, Hutchings TJ, Jiao P, Johnson L, Leung WY, Li PK, Steel GR, Thompson AS, Threadgill MD, Woodman TJ, Lloyd MD.
Ibuprofen and related 2-arylpropanoic acid (2-APA) drugs are often given as a racemic mixture and the R-enantiomers undergo activation in vivo by metabolic chiral inversion. The chiral inversion pathway consists of conversion of the drug to the coenzyme A ester (by an acyl-CoA synthetase) followed by chiral inversion by α-methylacyl-CoA racemase (AMACR; P504S). The enzymes responsible for hydrolysis of the product S-2-APA-CoA ester to the active S-2-APA drug have not been identified. In this study, conversion of a variety of 2-APA-CoA esters by human acyl-CoA thioesterase-1 and -2 (ACOT-1 and -2) was investigated. Human recombinant ACOT-1 and -2 (ACOT-1 and -2) were both able to efficiently hydrolyse a variety of 2-APA-CoA substrates. Studies with the model substrates R- and S-2-methylmyristoyl-CoA showed that both enzymes were able to efficiently hydrolyse both of the epimeric substrates with (2R)- and (2S)- methyl groups. ACOT-1 is located in the cytosol and is able to hydrolyse 2-APA-CoA esters exported from the mitochondria and peroxisomes for inhibition of cyclo-oxygenase-1 and -2 in the endoplasmic reticulum. It is a prime candidate to be the enzyme responsible for the pharmacological action of chiral inverted drugs. ACOT-2 activity may be important in 2-APA toxicity effects and for the regulation of mitochondrial free coenzyme A levels. These results support the idea that 2-APA drugs undergo chiral inversion via a common pathway.
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