title: Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK-3-β activation to enhance protein degradation and attenuate nuclear translocation of β-catenin.
abstract: The aim of our study was to investigate the mechanisms by which rhubarb regulates β-catenin as well as metastasis of hepatocellular carcinomas. Our results revealed that rhubarb extract inhibited HA22T cell migration ability in wound healing, migration and invasion assays in a dose-dependent manner. Rhubarb also reduced β-catenin protein level, downregulated its downstream proteins, cyclin D, Tbx3 and c-Myc, and attenuated the expression of MMP9 and contactin-1 metastatic factors. Additionally, rhubarb inhibited β-catenin nuclear accumulation and induced its degradation via proteasome-mediated pathway. Furthermore, we found that rhubarb suppressed the p-ser(9) GSK-3-β protein level to inactivate Wnt signalling and reduce β-catenin protein level. Taken together; we found that rhubarb blocked the metastatic process of HA22T hepatocellular carcinoma cells mediated through GSK-3-β activation, and enhancement of protein degradation as well as reduction of the nuclear accumulation of β-catenin.
authors.affiliation: Department of Emergency Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan.
authors.forename: Kun-Hsi
authors.initials: KH
authors.lastname: Tsai
authors.forename: Hau-Hsueh
authors.initials: HH
authors.lastname: Hsien
authors.forename: Li-Mien
authors.initials: LM
authors.lastname: Chen
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Ting
authors.forename: Yuh-Shyong
authors.initials: YS
authors.lastname: Yang
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage*; D059748:Proteolysis / Q000187:drug effects; D012250:Rheum / Q000737:chemistry*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D051176:beta Catenin; D038362:Glycogen Synthase Kinase 3