Department of Food Chemistry, Technology and Biotechnology, Gdansk University of Technology, Narutowicza St. 11/12, 80-233, Gdansk, Poland.
Department of Nutritional Toxicology, German Institute of Human Nutrition, Potsdam-Rehbrücke, 14558, Nuthetal, Germany.
Sci Rep. 2022 Mar 22;12(1):4875. doi: 10.1038/s41598-022-08893-8.
Chemopreventive properties of Brassica vegetables are attributed mainly to their characteristic compounds-glucosinolates (GLs) and their main hydrolysis products-isothiocyanates (ITCs) and indoles. In this study, we compared antiproliferative activity (MTT test in HT29 cells) and genotoxic effects (comet assay in HT29 cells and restriction analysis in a cell-free system) of three GLs (sinigrin (SIN), glucotropaeolin (GTL), and glucobrassicin (GLB)) with that of their major degradation products. Intact GLs did not exhibit cytotoxic activity, possibly due to their limited bioavailability. However, in the presence of myrosinase (MYR), GLs gained the ability to inhibit HT29 cells' growth. The addition of MYR caused the hydrolysis of GLs to the corresponding ITCs or indoles, i.e. compounds that show stronger biological activity than parent GLs. Pure ITC/indole solutions showed the strongest antiproliferative activity. Based on the results of restriction analysis, it was found that GLs to a greater extent than ITCs caused DNA modification in a cell-free system. In the case of GLs, metabolic activation by the S9 fraction increased this effect, and at the same time changed the preferential binding site from the area of base pairs AT to GC base pairs. Of all compounds tested, only benzyl ITC caused DNA damage detectable in the comet assay, but it required relatively high concentrations.
十字花科蔬菜的化学预防特性主要归因于其特征化合物——硫代葡萄糖苷（GLs）及其主要水解产物——异硫氰酸酯（ITCs）和吲哚。在这项研究中，我们比较了三种 GLs（黑芥子硫苷酸钾（SIN）、葡萄糖硫苷（GTL）和葡萄糖异硫氰酸盐（GLB））及其主要降解产物的抗增殖活性（MTT 试验在 HT29 细胞中）和遗传毒性（彗星试验在 HT29 细胞和无细胞系统中的限制分析）。完整的 GLs 没有表现出细胞毒性活性，这可能是由于其生物利用度有限。然而，在存在黑芥子酶（MYR）的情况下，GLs 获得了抑制 HT29 细胞生长的能力。添加 MYR 导致 GLs 水解为相应的 ITCs 或吲哚，即比母体 GLs 具有更强生物学活性的化合物。纯 ITC/吲哚溶液显示出最强的抗增殖活性。根据限制分析的结果，发现 GLs 比 ITCs 更能在无细胞系统中引起 DNA 修饰。在 GLs 的情况下，S9 部分的代谢激活增加了这种效应，同时改变了优先结合位点从碱基对 AT 到 GC 碱基对。在所测试的所有化合物中，只有苄基 ITC 能在彗星试验中检测到 DNA 损伤，但它需要相对较高的浓度。
