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黄酮抑制乳腺癌细胞中的一氧化氮合酶(NOS)活性、一氧化氮生成及蛋白质S-亚硝基化。

Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells.

作者信息

Zhu Wenzhen, Yang Bingwu, Fu Huiling, Ma Long, Liu Tingting, Chai Rongfei, Zheng Zhaodi, Zhang Qunye, Li Guorong

机构信息

Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014, China.

Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.

出版信息

Biochem Biophys Res Commun. 2015 Mar 13;458(3):590-595. doi: 10.1016/j.bbrc.2015.01.154. Epub 2015 Feb 11.

Abstract

As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by "Biotin-switch" method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone.

摘要

作为黄酮类化合物的核心结构,黄酮已被证明具有抗癌作用。黄酮的生长抑制功能与一氧化氮(NO)有关。NO由一氧化氮合酶(NOS)合成,并且在多种癌细胞中通常会增加。NO通过S-亚硝基化调节多种细胞反应。在本研究中,我们探讨了黄酮对乳腺癌细胞中一氧化氮(NO)相关细胞过程的诱导调节作用。我们的结果表明,黄酮抑制乳腺癌细胞增殖并诱导凋亡。黄酮通过剂量依赖性抑制NOS酶活性来抑制NO合成。通过荧光显微镜和流式细胞术检测到NO生成的减少。黄酮对NOS活性的诱导抑制作用取决于完整的细胞结构。对于NO诱导的蛋白质修饰,黄酮处理显著下调了蛋白质S-亚硝基化,这是通过“生物素开关”方法检测到的。本研究为黄酮的抗癌功能提供了一种新的、与NO相关的机制。

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