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脂肪酸及其脂质介质在癌细胞凋亡诱导中的作用。

Fatty acids and their lipid mediators in the induction of cellular apoptosis in cancer cells.

作者信息

Biswas Pritam, Datta Chandreyee, Rathi Parul, Bhattacharjee Ashish

机构信息

Department of Biotechnology, National Institute of Technology, Durgapur 713209, West Bengal, India.

Department of Biotechnology, National Institute of Technology, Durgapur 713209, West Bengal, India.

出版信息

Prostaglandins Other Lipid Mediat. 2022 Jun;160:106637. doi: 10.1016/j.prostaglandins.2022.106637. Epub 2022 Mar 24.

Abstract

The oxygenation of polyunsaturated fatty acids such as arachidonic and linoleic acid through enzymes like lipoxygenases (LOXs) are common and often leads to the production of various bioactive lipids that are important both in acute inflammation and its resolution and thus in disease progression. Amongst the several isoforms of LOX that are expressed in mammals, 15-lipoxygenase (15-LOX) has shown to be crucial in the context of inflammation. Moreover, being expressed in cells of the immune system, as well as in epithelial cells; the enzyme has been shown to crosstalk with a number of important signalling pathways. Mounting evidences from recent reports suggest that 15-LOX has anti-cancer activities which are dependent or independent of its metabolites, and is executed through several downstream pathways like cGMP, PPAR, p53, p21 and NAG-1. However, it is still unclear whether the up-regulation of 15-LOX is associated with cancer cell apoptosis. Monoamine oxidase A (MAO-A), on the other hand, is a mitochondrial flavoenzyme which is believed to be involved in the pathogenesis of atherosclerosis and inflammation and in many other neurological disorders. MAO-A has also been reported as a potential therapeutic target in different types of cancers like prostate cancer, lung cancer etc. In this review, we discussed about the role of fatty acids and their lipid mediators in cancer cell apoptosis. Here we particularly focused on the contribution of oxidative enzymes like 15-LOX and MAO-A in mediating apoptosis in lung cancer cell after fatty acid induction.

摘要

多不饱和脂肪酸(如花生四烯酸和亚油酸)通过脂氧合酶(LOXs)等酶进行氧化是常见的现象,并且常常导致各种生物活性脂质的产生,这些脂质在急性炎症及其消退过程中都很重要,因而在疾病进展中也起着重要作用。在哺乳动物中表达的几种LOX同工型中,15-脂氧合酶(15-LOX)已被证明在炎症背景下至关重要。此外,该酶在免疫系统细胞以及上皮细胞中均有表达,已显示它能与许多重要的信号通路相互作用。近期报告的越来越多的证据表明,15-LOX具有抗癌活性,这种活性依赖或不依赖于其代谢产物,并通过cGMP、PPAR、p53、p21和NAG-1等几种下游途径发挥作用。然而,15-LOX的上调是否与癌细胞凋亡相关仍不清楚。另一方面,单胺氧化酶A(MAO-A)是一种线粒体黄素酶,被认为与动脉粥样硬化和炎症的发病机制以及许多其他神经疾病有关。MAO-A也被报道为前列腺癌、肺癌等不同类型癌症的潜在治疗靶点。在本综述中,我们讨论了脂肪酸及其脂质介质在癌细胞凋亡中的作用。在这里,我们特别关注了15-LOX和MAO-A等氧化酶在脂肪酸诱导后介导肺癌细胞凋亡中的作用。

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