Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Dúbravská cesta 9, 84505 Bratislava, Slovakia.
Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, 84215 Bratislava, Slovakia.
Molecules. 2022 Apr 19;27(9):2622. doi: 10.3390/molecules27092622.
Thymol affects various types of tumor cell lines, including colorectal cancer cells. However, the hydrophobic properties of thymol prevent its wider use. Therefore, new derivatives (acetic acid thymol ester, thymol β-D-glucoside) have been synthesized with respect to hydrophilic properties. The cytotoxic effect of the new derivatives on the colorectal cancer cell lines HT-29 and HCT-116 was assessed via MTT assay. The genotoxic effect was determined by comet assay and micronucleus analysis. ROS production was evaluated using ROS-Glo™ HO Assay. We confirmed that one of the thymol derivatives (acetic acid thymol ester) has the potential to have a cyto/genotoxic effect on colorectal cancer cells, even at much lower (IC0.08 μg/mL) concentrations than standard thymol (IC60 μg/mL) after 24 h of treatment. On the other side, the genotoxic effect of the second studied derivative-thymol β-D-glucoside was observed at a concentration of about 1000 μg/mL. The antiproliferative effect of studied derivatives of thymol on the colorectal cancer cell lines was found to be both dose- and time-dependent at 100 h. Moreover, thymol derivative-treated cells did not show any significantly increased rate of micronuclei formation. New derivatives of thymol significantly increased ROS production too. The results confirmed that the effect of the derivative on tumor cells depends on its chemical structure, but further detailed research is needed. However, thymol and its derivatives have great potential in the prevention and treatment of colorectal cancer, which remains one of the most common cancers in the world.
百里香酚影响多种类型的肿瘤细胞系，包括结直肠癌细胞。然而，百里香酚的疏水性使其应用受到限制。因此，人们针对其亲水性合成了新的衍生物（乙酸百里香酚酯、百里香酚-β-D-葡萄糖苷）。通过 MTT 测定法评估了新衍生物对结直肠癌细胞系 HT-29 和 HCT-116 的细胞毒性作用。通过彗星试验和微核分析测定遗传毒性作用。使用 ROS-Glo™ HO 测定法评估 ROS 产生。我们证实，百里香酚的一种衍生物（乙酸百里香酚酯）在治疗 24 小时后，即使在比标准百里香（IC 60 μg/mL）低得多的浓度（IC 0.08 μg/mL）下，也有可能对结直肠癌细胞产生细胞毒性/遗传毒性作用。另一方面，第二种研究的衍生物——百里香酚-β-D-葡萄糖苷在约 1000 μg/mL 的浓度下观察到遗传毒性作用。在 100 小时时，研究的百里香酚衍生物对结直肠癌细胞系的增殖抑制作用呈剂量和时间依赖性。此外，用研究的百里香酚衍生物处理的细胞没有显示出微核形成率有任何显著增加。新的百里香酚衍生物也显著增加了 ROS 的产生。研究结果证实，该衍生物对肿瘤细胞的作用取决于其化学结构，但还需要进一步的详细研究。然而，百里香酚及其衍生物在预防和治疗结直肠癌方面具有巨大的潜力，结直肠癌仍然是世界上最常见的癌症之一。
