Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia.
Neoplasma. 2024 Apr;71(2):193-200. doi: 10.4149/neo_2024_231222N658.
Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high mortality rate. In the last few years, attention has been focused on substances of natural origin with anticancer activity. One such substance is thymol and its derivatives, which have been shown to have an antitumor effect also against CRC cells. In our study, we focused on determining the biological and antibacterial effects of thymol and thymol derivatives. Analyses were performed on a 3D model of human colon carcinoma cell lines (HCT-116 and HT-29) - spheroids. The cytotoxic (MTT assay) and genotoxic effect (comet assay) of thymol and derivatives: acetic acid thymol ester and thymol ß-D-glucoside were determined. ROS levels (ROS-Glo™ H2O2 Assay) and total antioxidant status (Randox TAS Assay) were also monitored. Last but not least, we also detected the effect of the derivatives using a disk diffusion assay and determined the number of colonies on the plates on selected bacteria such as Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, Lacticaseibacillus paracasei, Lactobacillus brevis, Lactobacillus pentosus and Weizmannia coagulans. The derivatives did not show a significant inhibitory effect on the growth of LAB bacteria (lactic acid bacteria) in contrast to thymol. Overall, thymol derivatives are cytotoxic, genotoxic and increase ROS levels. Among the derivatives tested, acetic acid thymol ester (IC50 ~ 0.2 μg/ml) was more effective. The second derivative tested (thymol β-D-glucoside) was effective at higher concentrations than thymol. Our research confirmed that thymol derivatives have a toxic effect on the 3D model of intestinal tumor cells, while they do not have a toxic effect on selected intestinal bacteria. Thus, they could bring new significance to the prevention or treatment of CRC.
结直肠癌（CRC）是最常见的恶性肿瘤之一，死亡率很高。在过去的几年中，人们一直关注具有抗癌活性的天然来源物质。其中一种物质是百里香酚及其衍生物，已证明其对 CRC 细胞也具有抗肿瘤作用。在我们的研究中，我们专注于确定百里香酚和其衍生物的生物学和抗菌作用。分析是在人类结肠癌细胞系（HCT-116 和 HT-29）-球体的 3D 模型上进行的。测定了百里香酚和衍生物（乙酸百里香酯和百里香β-D-葡萄糖苷）的细胞毒性（MTT 测定）和遗传毒性（彗星试验）。还监测了 ROS 水平（ROS-Glo™ H2O2 测定）和总抗氧化状态（Randox TAS 测定）。最后但同样重要的是，我们还使用圆盘扩散测定法检测了衍生物的作用，并在选定的细菌（如鼠李糖乳杆菌、植物乳杆菌、副干酪乳杆菌、短乳杆菌、戊糖片球菌和魏茨曼氏球菌）的平板上测定了菌落数。与百里香酚相比，衍生物对 LAB 细菌（乳酸菌）的生长没有表现出显著的抑制作用。总的来说，百里香酚衍生物具有细胞毒性、遗传毒性并增加 ROS 水平。在所测试的衍生物中，乙酸百里香酚酯（IC50~0.2μg/ml）更有效。测试的第二种衍生物（百里香β-D-葡萄糖苷）在较高浓度下比百里香更有效。我们的研究证实，百里香酚衍生物对肠道肿瘤细胞的 3D 模型具有毒性作用，而对选定的肠道细菌则没有毒性作用。因此，它们可能为 CRC 的预防或治疗带来新的意义。
