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黄酮类化合物与 DNA 结合效能与其诱导的细胞损伤的相关性。

Correlation of binding efficacies of DNA to flavonoids and their induced cellular damage.

机构信息

Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, BF-142, Salt lake, Sector-I, Kolkata 700 064, India.

Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, BF-142, Salt lake, Sector-I, Kolkata 700 064, India.

出版信息

J Photochem Photobiol B. 2017 May;170:256-262. doi: 10.1016/j.jphotobiol.2017.04.019. Epub 2017 Apr 19.

DOI:10.1016/j.jphotobiol.2017.04.019
PMID:28456117
Abstract

Flavonoids are dietary intakes which are bestowed with several health benefits. The most studied property of flavonoids is their antioxidant efficacy. Among the chosen flavonoids Quercetin, Kaempferol and Myricetin is catagorized as flavonols whereas Apigenin and Luteolin belong to the flavone group. In the present study anti-cancer properties of flavonoids are investigated on the basis of their binding efficacy to ct-DNA and their ability to induce cytotoxicity in K562 leukaemic cells. The binding affinities of the flavonoids with calf thymus DNA (ct-DNA) are in the order Quercetin>Myricetin>Luteolin>Kaempferol>Apigenin. Quercetin with fewer OH than myricetin has higher affinity towards DNA suggesting that the number and position of OH influence the binding efficacies of flavonoids to ct-DNA. CD spectra and EtBr displacement studies evidence myricetin and apigenin to be stronger intercalators of DNA compared to quercetin. From comet assay results it is observed that quercetin and myricetin when used in combination induce higher DNA damage in K562 leukemic cells than when tested individually. Higher binding efficacy has been recorded for quercetin to DNA at lower pH, which is the micro environment of cancerous cells, and hence quercetin can act as a potential anti-cancer agent. Presence of Cu also increases cellular damage as recorded by comet assay.

摘要

类黄酮是一种具有多种健康益处的饮食摄入物。类黄酮最被研究的特性是其抗氧化功效。在所选择的类黄酮中,槲皮素、山奈酚和杨梅素被归类为黄酮醇,而芹菜素和木犀草素属于黄酮类。在本研究中,基于类黄酮与 ct-DNA 的结合效力及其在 K562 白血病细胞中诱导细胞毒性的能力来研究类黄酮的抗癌特性。类黄酮与小牛胸腺 DNA(ct-DNA)的结合亲和力顺序为槲皮素>杨梅素>木犀草素>山奈酚>芹菜素。与杨梅素相比,OH 较少的槲皮素有更高的 DNA 亲和力,这表明 OH 的数量和位置影响类黄酮与 ct-DNA 的结合效力。CD 光谱和 EtBr 置换研究表明,与槲皮素相比,杨梅素和芹菜素是更强的 DNA 嵌入剂。从彗星试验结果可以看出,当与单独测试相比时,槲皮素和杨梅素联合使用时在 K562 白血病细胞中诱导更高的 DNA 损伤。在较低的 pH 值下,即癌细胞的微环境,观察到类黄酮与 DNA 的结合效力更高,因此槲皮素可以作为一种潜在的抗癌剂。彗星试验也记录到 Cu 的存在会增加细胞损伤。

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