Physcion 8-O-β-glucopyranoside prevents hypoxia-induced epithelial-mesenchymal transition in colorectal cancer HCT116 cells by modulating EMMPRIN

Abstract

Epithelial-mesenchymal transition (EMT) is considered as the most important mechanism that underlies the initiation of cancer metastasis. Here we report that Physicon 8-O-β-glucopyranoside (PG), a major active ingredient from a traditional Chinese herbal medicine Rumex japonicus Houtt, is capable of preventing human colorectal cancer cells from hypoxia-induced EMT. The treatment of the cells with PG reversed the EMT-related phenotype that has the morphological changes, down-regulation of E-cadherin, and hypoxia-induced cell migration and invasion. The effect was mediated at least in part by inhibiting the mRNA and protein expressions of EMMPRIN via modulation of PTEN/Akt/HIF-1α pathway. In addition, we found that PG-mediated prevention of EMT involved blockade of the hypoxia-induced up-regulation of Snail, Slug and Twist. In summary, this study showed that PG can prevent EMT induced by hypoxia, the environment that commonly exists in the center of a solid tumor. Given the low toxicity of PG to the healthy tissues, our study suggests that PG can serve as a safe therapeutic agent for suppressing cancer metastasis.

Keywords: EMMPRIN.; EMT; colorectal cancer; hypoxia; physcion 8-O-β-glucopyranoside.