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苦玄参苷 I 对癌细胞和正常细胞的细胞毒性、遗传毒性和 DNA 保护作用的比较。

Comparison of Cytotoxic, Genotoxic, and DNA-Protective Effects of Skyrin on Cancerous vs. Non-Cancerous Human Cells.

机构信息

Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovičova 6, 842 15 Bratislava, Slovakia.

Cancer Research Institute, Biomedical Research Centre of the Slovak Academy of Sciences, Dúbravská Cesta 9, 845 05 Bratislava, Slovakia.

出版信息

Int J Mol Sci. 2022 May 10;23(10):5339. doi: 10.3390/ijms23105339.

DOI:10.3390/ijms23105339
PMID:35628149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9142076/
Abstract

Secondary metabolites as a potential source of anticancer therapeutics have been the subject of many studies. Since hypericin, a metabolite isolated from L., shows several biomedical properties applicable in oncology, the aim of our study was to investigate its potential precursor skyrin in terms of genotoxic and DNA-protective effects. These skyrin effects were analyzed by cell-free methods, and cytotoxicity was estimated by an MTT assay and by a trypan blue exclusion test, while the genotoxic/antigenotoxic potential was examined by comet assay using non-cancerous human lymphocytes and the HepG2 cancer cell line. Skyrin did not show DNA-damaging effects but rather exhibited DNA-protectivity using a DNA-topology assay. However, we observed only weak antioxidant and chelating skyrin properties in other cell-free methods. Regarding the cytotoxic activity of skyrin, HepG2 cells were more prone to skyrin-induced death in comparison to human lymphocytes. Skyrin in non-cytotoxic concentrations did not exhibit elevated genotoxicity in both cell types. On the other hand, skyrin displayed moderate DNA-protective effects that were more noticeable in the case of non-cancerous human lymphocytes. The potential genotoxic effects of skyrin were not observed, and its DNA-protective capacity was more prominent in non-cancerous cells. Therefore, skyrin might be a promising agent used in anticancer therapy.

摘要

次生代谢产物作为抗癌治疗的潜在来源，一直是许多研究的主题。由于从 L. 中分离出的代谢产物金丝桃素具有多种适用于肿瘤学的生物医学特性，因此我们的研究目的是研究其潜在前体酪醇在遗传毒性和 DNA 保护作用方面的潜力。通过无细胞方法分析了酪醇的这些作用，并用 MTT 测定法和台盼蓝排除试验估计了细胞毒性，同时使用非癌细胞系人淋巴细胞和 HepG2 癌细胞系的彗星试验分析了遗传毒性/抗原毒性潜力。酪醇没有显示出 DNA 损伤作用，而是在 DNA 拓扑结构测定中显示出 DNA 保护作用。然而，我们仅在其他无细胞方法中观察到较弱的抗氧化和螯合酪醇特性。关于酪醇的细胞毒性活性，与人类淋巴细胞相比，HepG2 细胞更容易受到酪醇诱导的死亡。在两种细胞类型中，非细胞毒性浓度的酪醇均未显示出升高的遗传毒性。另一方面，酪醇显示出适度的 DNA 保护作用，在非癌细胞中更为明显。未观察到酪醇的潜在遗传毒性作用，并且在非癌细胞中其 DNA 保护能力更为突出。因此，酪醇可能是一种有前途的抗癌治疗药物。

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