Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China.
Biomed Res Int. 2020 Jan 30;2020:7643248. doi: 10.1155/2020/7643248. eCollection 2020.
Germacrone, a natural 10-membered monocyclic sesquiterpene with three double bonds and a ketone, was isolated from the roots of traditional Chinese medicine (SC). The pharmacological value and intrinsic mechanism of germacrone in the treatment of esophageal squamous cell carcinoma (ESCC) are still unclear. Therefore, in this study, we further explored the internal molecular mechanism by which germacrone exerts its antiproliferation and antimigration ability against ESCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assays showed that germacrone dose-dependently inhibited the proliferation of ESCC cells. Flow cytometry analysis (FACS) and wound healing experiments on germacrone treated ESCC cells showed that germacrone could induce apoptosis and inhibit the migration of ESCC cells in a dose-dependent manner. In the study on the mechanism of action of germacrone in antiesophageal cancer, we found that germacrone increased the ratio of Bax/Bcl-2 in the cytoplasm of ESCC, resulting in the activation of Caspase-9 and Caspase-3 and decreased the expression of Grp78, thereby reducing the inhibition of Caspase-12 and Caspase-7. In addition, we found that germacrone also inhibited STAT3 phosphorylation in a dose-dependent manner. In conclusion, we determined that germacrone exerted an antiesophageal effect through intrinsic apoptotic signaling pathways and by inhibiting STAT3 activity in ESCC cells.
倍半萜Germacrone 是一种天然的 10 元单环倍半萜，具有三个双键和一个酮基，从中药（SC）的根部分离得到。Germacrone 治疗食管鳞状细胞癌（ESCC）的药理价值和内在机制尚不清楚。因此，在这项研究中，我们进一步探讨了 Germacrone 发挥其抗增殖和抗迁移能力的内在分子机制，以治疗 ESCC。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）检测结果表明，Germacrone 呈剂量依赖性抑制 ESCC 细胞的增殖。对 Germacrone 处理的 ESCC 细胞进行流式细胞术分析（FACS）和划痕愈合实验表明，Germacrone 可以诱导细胞凋亡，并呈剂量依赖性抑制 ESCC 细胞的迁移。在 Germacrone 抗食管癌作用机制的研究中，我们发现 Germacrone 增加了 ESCC 细胞质中 Bax/Bcl-2 的比值，导致 Caspase-9 和 Caspase-3 的激活，并降低了 Grp78 的表达，从而减少了对 Caspase-12 和 Caspase-7 的抑制。此外，我们发现 Germacrone 还呈剂量依赖性抑制 STAT3 磷酸化。总之，我们确定 Germacrone 通过内在凋亡信号通路和抑制 ESCC 细胞中的 STAT3 活性发挥抗食管作用。
