科学家揭示布洛芬抗癌机制

毒手药王邓智先

科学家揭示布洛芬抗癌机制


作者：佚名时间：2013-9-29编辑：杨帆
导语：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。

标签：布洛芬  抗肿瘤  手性

　　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，我们重点研究了手性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。

原文链接：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
Abstract
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.

小洁

布洛芬还有这样的用处，这个还真的不知道

刘永利

布洛芬的作用还真大呀

胜利者

还有这功效？

yyz

是真的吗？