Aydın Adnan Menderes University, Faculty of Science, Department of Biology, Central Campus, Aydın, Turkey.
Aydın Adnan Menderes University, Faculty of Science, Department of Biology, Central Campus, Aydın, Turkey.
Toxicol In Vitro. 2023 Dec;93:105694. doi: 10.1016/j.tiv.2023.105694. Epub 2023 Sep 11.
In this study, the anticancer activity of umbelliferone (7-hydroxycoumarin-UMB) was investigated in MKN-45 human gastric cancer and MIA PaCa-2 human pancreatic cancer cells. The cytotoxic effect of UMB on MKN-45 and MIA PaCa-2 cells was determined by WST-8 cell viability assay; the effect on colony formation and migration potential by colony forming assay and wound healing/cell migration assay. Apoptotic effect of UMB was determined by measuring the change in mitochondrial membrane potentials, reactive oxygen species levels, and Caspase-3 activities in cells. Anticancer drugs cisplatin and gemcitabine were used as positive controls in experiments, and NIH/Swiss 3 T3 mouse embryonic fibroblast cells were used as a healthy cell group. The results of this study showed that umbelliferone had a significant cytotoxic effect in MKN-45 and MIA PaCa-2 cells, especially after 72 h treatment, while its cytotoxic effect in NIH/3 T3 cells was low. Furthermore, UMB reduces significantly the potential of cells to colonize and migrate; it has been determined that it causes apoptosis by decreasing the mitochondrial membrane potential, increasing intracellular ROS levels and Caspase-3 activity. UMB was found to have more anticancer effect on MIA PaCa-2 cells compared to MKN-45 cells. This showed that UMB has a cell-selective effect.
在这项研究中，研究了伞形酮（7-羟基香豆素-UMB）对人胃癌 MKN-45 细胞和人胰腺癌细胞 MIA PaCa-2 的抗癌活性。通过 WST-8 细胞活力测定法测定 UMB 对 MKN-45 和 MIA PaCa-2 细胞的细胞毒性作用；通过集落形成测定法和划痕愈合/细胞迁移测定法测定对集落形成和迁移潜力的影响。通过测量细胞中线粒体膜电位、活性氧水平和 Caspase-3 活性的变化来确定 UMB 的促凋亡作用。顺铂和吉西他滨等抗癌药物在实验中用作阳性对照，NIH/3T3 瑞士鼠胚胎成纤维细胞用作健康细胞组。研究结果表明，UMB 对 MKN-45 和 MIA PaCa-2 细胞具有显著的细胞毒性作用，尤其是在 72 小时处理后，而其对 NIH/3T3 细胞的细胞毒性作用较低。此外，UMB 显著降低了细胞的定植和迁移潜力；通过降低线粒体膜电位、增加细胞内 ROS 水平和 Caspase-3 活性，确定其引起细胞凋亡。与 MKN-45 细胞相比，UMB 对 MIA PaCa-2 细胞具有更强的抗癌作用。这表明 UMB 具有细胞选择性作用。
