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评估蓝莓类黄酮、槲皮素、山柰酚和龙胆酸通过氧化应激和凋亡参数对 HCT-116 细胞的抗癌潜力。

Assessing Anticancer Potential of Blueberry Flavonoids, Quercetin, Kaempferol, and Gentisic Acid, Through Oxidative Stress and Apoptosis Parameters on HCT-116 Cells.

机构信息

Department of Medical Biochemistry, Faculty of Medicine, Ege University, Bornova, Turkey.

Department of Medical Biology, Faculty of Medicine, Ege University, Bornova, Turkey.

出版信息

J Med Food. 2019 Nov;22(11):1118-1126. doi: 10.1089/jmf.2019.0098. Epub 2019 Jun 26.

DOI:10.1089/jmf.2019.0098
PMID:31241392
Abstract

In recent years, natural products gained popularity with their anti-inflammatory and antioxidant effects mediated by chemical compounds within their composition. Study results offering them as palliative therapy options in cancer or as anticancer agents with high levels of cytotoxicity brought a new approach to combine cancer treatment protocols with these products. From a different perspective, edible types of these products are suggested in daily diets due to their potential cancer preventive effects. Our preliminary work was on blueberry extracts () as a main representative of these natural products, and the contents of the extracts were analyzed with liquid chromatography tandem mass spectrometry (LC MS/MS) to reveal the composition and distribution of polyphenolic compounds within. The most abundant polyphenols detected in extracts were quercetin, kaempferol, and a phenolic acid, gentisic acid (GA). The compounds were further evaluated on treated HCT-116 cells for their potential anticancer effects by measuring total antioxidant status, total oxidant status, and 8-hydroxydeoxyguanosine levels for evaluation of oxidative stress and through protein array analysis and flow cytometric analysis for evaluation of apoptosis. In analysis of oxidative stress parameters, reduced total oxidant levels and reduced oxidative stress index levels were found in cells treated with the compounds in comparison with untreated cells. In apoptosis-related protein profiles, at least twofold reduction in various apoptotic proteins was observed after quercetin and kaempferol treatment, whereas a different profile was observed for GA. Overall, results of this study showed that quercetin and kaempferol have strong cytotoxic, antioxidant, and apoptotic effects, although GA is mostly effective as an antioxidant polyphenol on HCT-116 cells.

摘要

近年来,天然产物因其成分中的化学化合物具有抗炎和抗氧化作用而受到关注。研究结果表明,它们可以作为癌症的姑息治疗选择,或作为具有高细胞毒性的抗癌药物,为将癌症治疗方案与这些产品结合提供了一种新方法。从另一个角度来看,由于这些产品具有潜在的抗癌作用,建议在日常饮食中食用这些产品的可食用类型。我们的初步工作是研究蓝莓提取物()作为这些天然产物的主要代表,并用液相色谱串联质谱(LC-MS/MS)分析提取物的成分,以揭示多酚化合物在其中的组成和分布。在提取物中检测到的最丰富的多酚是槲皮素、山柰酚和一种酚酸,即没食子酸(GA)。进一步评估了这些化合物对 HCT-116 细胞的潜在抗癌作用,方法是通过测量总抗氧化状态、总氧化状态和 8-羟基脱氧鸟苷水平来评估氧化应激,并通过蛋白质阵列分析和流式细胞术分析来评估细胞凋亡。在氧化应激参数分析中,与未处理的细胞相比,用这些化合物处理的细胞中的总氧化剂水平和氧化应激指数水平降低。在细胞凋亡相关蛋白谱中,在用槲皮素和山柰酚处理后,至少有两种凋亡蛋白的水平降低,而 GA 则表现出不同的谱。总的来说,这项研究的结果表明,槲皮素和山柰酚具有很强的细胞毒性、抗氧化和促凋亡作用,而 GA 主要作为抗氧化多酚对 HCT-116 细胞有效。

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