Abstract
Germacrone, a natural 10-membered monocyclic sesquiterpene with three double bonds and a ketone, was isolated from the roots of traditional Chinese medicine Saussurea costus (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.
Highlights
Esophageal cancer is the ninth most common cancer in the world
Germacrone Inhibits esophageal squamous cell carcinoma (ESCC) Cell Proliferation. e effect of germacrone on the viabilities of Eca109 and EC9706 cells was examined by MTT assay. e results revealed that the proliferation of both cell lines were inhibited by germacrone in dose- and time-dependent manners (Figures 1(a) and 1(b)). e IC50 values at 12, 24, and 48 h posttreatment were 34.38, 25.95, and 15.23 μg/mL for Eca109 cells and 38.26, 28.34, and 17.19 μg/mL for EC9706 cells, respectively. is suggested that Eca109 cells were slightly more sensitive to germacrone induced growth inhibition than EC9706 cells
Caspase-3 may be activated through the endoplasmic reticulum apoptosis pathway, so we studied the effect of germacrone on the endoplasmic reticulum of ESCC cells
Summary
Types of esophageal cancer include esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) [1]. About 572,000 new cases of esophageal cancer are diagnosed each year and over 509,000 deaths are estimated to be due to esophageal cancer [1]. E 5-year survival rate of patients with ESCC was only 10% [3]. In 2012, the number of deaths due to ESCC accounted for 5% of all cancer deaths [4]. ESCC accounts for 80% of esophageal cancer cases worldwide and is the primary histological subtype [5]. Since there are no early symptoms, ESCC is commonly diagnosed at an advanced stage. Poor efficacy, adverse drug reactions, and drug resistance are the biggest drawbacks to systemic chemotherapy of ESCC. Poor efficacy, adverse drug reactions, and drug resistance are the biggest drawbacks to systemic chemotherapy of ESCC. erefore, clarification of its pathogenesis and identification of efficacious agents as new potential chemotherapeutic remedies for its prevention, diagnosis, and treatment are urgently needed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
