Gallic acid from Terminalia chebula inhibited the growth of esophageal carcinoma cells by suppressing the Hippo signal pathway

Document Type: Original Article

Authors

1 Department of Oncology, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028000, China

2 Department Oncology of Mongolian-Western Medicine, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028007, China

10.22038/ijbms.2020.42283.9982

Abstract

Objective(s): To explore the molecular mechanism of gallic acid (GA) from Terminalia chebula in suppressing the growth of esophageal carcinoma (EC).
Materials and Methods: Human EC cells (EC9706 and KYSE450) were treated with different concentrations of GA (10, 20, and 40 μg/ml), which were subjected to 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, plate clone formation assay, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining, and Western blotting. EC mice were divided into Model, 0.3% GA, and 1% GA groups to observe the tumor volume and the expressions of YAP, TAZ, Ki-67, and Caspase-3 in tumor tissues.
Results: GA decreased cell viability and colony formation of EC9706 and KYSE450 cells, which was more obvious as the concentration increased. In addition, GA promoted cell apoptosis in a concentration-dependent manner with the up-regulation of pro-apoptotic proteins (Bax, cleaved caspase-3, and cleaved caspase-9) and nuclear YAP/TAZ, as well as the down-regulation of anti-apoptotic protein Bcl-2 and the levels of p-YAP and p-TAZ. Moreover, GA decreased the growth of xenograft tumor in vivo, with the reduction in the tumor volume and the reduction of YAP and TAZ expressions in the tumor tissues. In addition, Ki-67 expression in GA groups was lower than those in the Model group, with the increase in caspase-3 expression in the tumor tissues. Changes aforementioned were obviously shown in the 0.3% GA group.
Conclusion: GA blocked the activity of the Hippo pathway to suppress cell proliferation of EC and facilitate cell apoptosis, which is expected to be a novel strategy for treatment of EC.

Keywords


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