Department of Physiology, Faculty of Medicine, Pamukkale University, 20160, Denizli, Turkey.
Department of Medical Biology, Faculty of Medicine, Ordu University, Ordu, Turkey.
Med Oncol. 2023 Aug 5;40(9):260. doi: 10.1007/s12032-023-02134-2.
There is an increasing incidence of liver cancer, which is a hazard for global health. The present study was designed to evaluate possible cytotoxic, genotoxic, apoptotic, oxidant and antioxidant effects of thymol on hepatocellular carcinoma (HepG2) cell line. The cytotoxic effect of thymol on HepG2 cell line was determined by XTT test. We also used the HUVEC cell line to show whether thymol damages healthy cells. Oxidative stress level was determined with Total Oxidant Status (TOS) and Total Antioxidant Status (TAS) measurement kits. Apoptosis of cells was detected in flow cytometry with Annexin V apoptosis kit. Apoptotic gene expressions were analyzed by real-time PCR. Genotoxicity was determined by comet assay, which measures DNA damage. The thymol IC dose was found to be 11 μM on HepG2 cell line. This dose had no lethal effect on the healthy HUVEC cell line. While thymol significantly decreased the TOS level, it increased the TAS level significantly in HepG2 cells compared to control. Thymol significantly induced apoptosis in HepG2 cells (apoptosis rate in control group 1%, in thymol group 21%). Thymol did not alter the gene expressions of bax, bcl-2, and casp3, all of which are associated with apoptosis. Statistically significant change in favor of genotoxicity was observed in tail length measurements. Our results suggest that thymol decreases oxidative stress in HepG2 cell line, but it induces apoptosis and genotoxicity.
肝癌发病率不断上升，对全球健康构成威胁。本研究旨在评估百里香酚对肝癌（HepG2）细胞系的潜在细胞毒性、遗传毒性、细胞凋亡、氧化应激和抗氧化作用。通过 XTT 试验测定百里香酚对 HepG2 细胞系的细胞毒性作用。我们还使用 HUVEC 细胞系来证明百里香酚是否会损害健康细胞。通过总氧化剂状态（TOS）和总抗氧化状态（TAS）试剂盒测定氧化应激水平。用 Annexin V 细胞凋亡试剂盒通过流式细胞术检测细胞凋亡。通过实时 PCR 分析凋亡基因的表达。通过彗星试验测定遗传毒性，该试验可测量 DNA 损伤。百里香酚对 HepG2 细胞系的 IC 剂量为 11 μM。该剂量对健康的 HUVEC 细胞系没有致死作用。与对照组相比，百里香酚显著降低了 HepG2 细胞中的 TOS 水平，同时显著增加了 TAS 水平。百里香酚显著诱导 HepG2 细胞凋亡（对照组凋亡率为 1%，百里香酚组为 21%）。百里香酚没有改变与细胞凋亡相关的 bax、bcl-2 和 casp3 的基因表达。在尾部长度测量方面观察到有利于遗传毒性的统计学显著变化。我们的研究结果表明，百里香酚降低了 HepG2 细胞系中的氧化应激，但诱导了细胞凋亡和遗传毒性。
