title: 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.
authors.forename: Z
authors.initials: Z
authors.lastname: Ding
authors.forename: F
authors.initials: F
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Tang
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Jiang
authors.forename: Z
authors.initials: Z
authors.lastname: Tang
authors.forename: H
authors.initials: H
authors.lastname: Wu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D051926:Basigin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D015687:Cell Hypoxia / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004642:Emodin / Q000031:analogs & derivatives* / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005960:Glucosides / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C497886:BSG protein, human; D005960:Glucosides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C000613896:physcion 8-O-glucopyranoside; D051926:Basigin; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D004642:Emodin
keywords: EMMPRIN.; EMT; colorectal cancer; hypoxia; physcion 8-O-β-glucopyranoside