title: Ginsenoside 20(S)-Rg3 targets HIF-1α to block hypoxia-induced epithelial-mesenchymal transition in ovarian cancer cells.
abstract: The prognosis of patients with ovarian cancer has remained poor mainly because of aggressive cancer progression. Since epithelial-mesenchymal transition (EMT) is an important mechanism mediating invasion and metastasis of cancer cells, targeting the EMT process with more efficacious and less toxic compounds to inhibit metastasis is of great therapeutic value for the treatment of ovarian cancer. We have found for the first time that the ginsenoside 20(S)-Rg3, a pharmacologically active component of the traditional Chinese herb Panax ginseng, potently blocks hypoxia-induced EMT of ovarian cancer cells in vitro and in vivo. Mechanistic studies confirm the mode of action of 20(S)-Rg3, which reduces the expression of hypoxia-inducible factor 1α (HIF-1α) by activating the ubiquitin-proteasome pathway to promote HIF-1α degradation. A decrease in HIF-1α in turn leads to up-regulation, via transcriptional suppression of Snail, of the epithelial cell-specific marker E-cadherin and down-regulation of the mesenchymal cell-specific marker vimentin under hypoxic conditions. Importantly, 20(S)-Rg3 effectively inhibits EMT in nude mouse xenograft models of ovarian cancer, promising a novel therapeutic agent for anticancer therapy.
authors.affiliation: Center for Translational Medicine, the First Affiliated Hospital School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Center for Translational Medicine, the First Affiliated Hospital School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Center for Translational Medicine, the First Affiliated Hospital School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Laboratory Medicine, the First Affiliated Hospital School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Gynaecology and Obstetrics, the First Affiliated Hospital School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pathology, the First Affiliated Hospital School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Huilian
authors.initials: H
authors.lastname: Hou
authors.affiliation: Center for Translational Medicine, the First Affiliated Hospital School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ding
authors.affiliation: Center for Translational Medicine, the First Affiliated Hospital School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059748:Proteolysis / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D036145:Ginsenosides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; C097367:ginsenoside Rg3