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NAD(P)H 脱氢酶醌 1(NQO1)途径综述。

Review on NAD(P)H dehydrogenase quinone 1 (NQO1) pathway.

机构信息

Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Sri Shivarathreeshwara Nagar, Mysuru, Karnataka, 570015, India.

出版信息

Mol Biol Rep. 2022 Sep;49(9):8907-8924. doi: 10.1007/s11033-022-07369-2. Epub 2022 Mar 28.

Abstract

NQO1 is an enzyme present in humans which is encoded by NQO1 gene. It is a protective antioxidant agent, versatile cytoprotective agent and regulates the oxidative stresses of chromatin binding proteins for DNA damage in cancer cells. The oxidization of cellular pyridine nucleotides causes structural alterations to NQO1 and changes in its capacity to binding of proteins. A strategy based on NQO1 to have protective effect against cancer was developed by organic components to enhance NQO1 expression. The quinone derivative compounds like mitomycin C, RH1, E09 (Apaziquone) and β-lapachone causes cell death by NQO1 reduction of two electrons. It was also known to be overexpressed in various tumor cells of breast, lung, cervix, pancreas and colon when it was compared with normal cells in humans. The mechanism of NQO1 by the reduction of FAD by NADPH to form FADH2 is by two ways to inhibit cancer cell development such as suppression of carcinogenic metabolic activation and prevention of carcinogen formation. The NQO1 exhibit suppression of chemical-mediated carcinogenesis by various properties of NQO1 which includes, detoxification of quinone scavenger of superoxide anion radical, antioxidant enzyme, protein stabilizer. This review outlines the NQO1 structure, mechanism of action to inhibit the cancer cell, functions of NQO1 against oxidative stress, drugs acting on NQO1 pathways, clinical significance.

摘要

NQO1 是一种存在于人体中的酶,由 NQO1 基因编码。它是一种保护性抗氧化剂、多功能细胞保护剂,可调节染色质结合蛋白的氧化应激,以防止癌细胞内的 DNA 损伤。细胞吡啶核苷酸的氧化会导致 NQO1 的结构改变,并改变其与蛋白质结合的能力。通过有机成分增强 NQO1 的表达,开发了一种基于 NQO1 的策略,以发挥其抗癌的保护作用。醌类衍生物化合物,如丝裂霉素 C、RH1、E09(阿帕齐醌)和β-拉帕醌,通过减少 NQO1 的两个电子来导致细胞死亡。与正常细胞相比,它在人类的各种乳腺癌、肺癌、宫颈癌、胰腺癌和结肠癌中过度表达。NQO1 通过 NADPH 将 FAD 还原为 FADH2 的机制是通过两种方式抑制癌细胞的发展,即抑制致癌代谢激活和预防致癌物形成。NQO1 通过其各种性质抑制化学介导的致癌作用,包括醌的解毒剂、超氧阴离子自由基的清除剂、抗氧化酶、蛋白质稳定剂。这篇综述概述了 NQO1 的结构、抑制癌细胞的作用机制、NQO1 对抗氧化应激的功能、作用于 NQO1 途径的药物以及临床意义。

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