Anti-esophageal Cancer Effect of Corilagin Extracted from Phmllanthi Fructus via the Mitochondrial and Endoplasmic Reticulum Stress Pathways

Abstract

Headings ethnopharmacological relevance: Corilagin (β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose) is a tannin isolated from the traditional ethnopharmacological plant Phmllanthi Fructus, which is widely used in not only traditional Chinese medicine but also tropical and subtropical medicine to ameliorate various diseases.

Aim of the study: This study was designed to isolate the potential anti-esophageal cancer (EC) component corilagin from Phmllanthi Fructus and explain its anti-EC mechanism.

Materials and methods: Corilagin was isolated from Phmllanthi Fructus by extraction and chromatographic procedures, and its anti-esophageal cancer effect was evaluated by in vitro and in vivo experiments. In vitro experiments included MTT analysis, flow cytometry, and the Transwell assay and were used to observe corilagin-mediated inhibition of EC cell growth. Western blotting was used to analyze the apoptotic pathway of EC cells. In vivo experiments used tumor-bearing nude mice to evaluate the antitumor effect of corilagin, and its potential mechanism was explored by Western blotting.

Results: Corilagin showed significant anti-EC activity in vitro and in vivo. Corilagin was significantly cytotoxic to EC cells and induced apoptosis in EC cells. Corilagin induced G0/G1 phase arrest by altering key G0/G1 cell cycle regulatory markers and significantly reducing the migration of EC cells and the number of cells in a time- and dose-dependent manner. Additionally, corilagin inhibited the growth of transplanted tumors in nude mice without significant toxicity. Regarding the anticancer mechanism of corilagin, the results showed that corilagin inhibited esophageal cancer progression by activating mitochondrial and endoplasmic reticulum stress signaling pathways.

Conclusions: Corilagin shows significant anti-EC activity in vitro and in vivo. The mechanism of the anti-EC activity of corilagin may be due to activating mitochondrial and endoplasmic reticulum stress signaling pathways.

Keywords: Apoptosis; Cytotoxicity; Esophageal cancer; Traditional Chinese medicine; Wound healing.