title: Aqueous extract of Polygonum bistorta modulates proteostasis by ROS-induced ER stress in human hepatoma cells.
abstract: Hepatocellular carcinoma (HCC) remains the leading cause of cancer mortality with limited therapeutic targets. The endoplasmic reticulum (ER) plays a pivotal role in maintaining proteostasis in normal cells. However, alterations in proteostasis are often found in cancer cells, making it a potential target for therapy. Polygonum bistorta is used in traditional Chinese medicine owing to its anticancer activities, but the molecular and pharmacological mechanisms remain unclear. Using hepatoma cells as a model system, this study demonstrated that P. bistorta aqueous extract (PB) stimulated ER stress by increasing autophagosomes but by blocking degradation, followed by the accumulation of ubiquitinated proteins and cell apoptosis. In addition, an autophagy inhibitor did not enhance ubiquitinated protein accumulation whereas a reactive oxygen species (ROS) scavenger diminished both ubiquitinated protein accumulation and ligand-stimulated epidermal growth factor receptor (EGFR) expression, suggesting that ROS generation by PB may be upstream of PB-triggered cell death. Nevertheless, PB-exerted proteostasis impairment resulted in cytoskeletal changes, impairment of cell adhesion and motility, and inhibition of cell cycle progression. Oral administration of PB delayed tumour growth in a xenograft model without significant body weight loss. These findings indicate that PB may be a potential new alternative or complementary medicine for HCC.
authors.affiliation: Graduate Institute of Integrated Medicine, China Medical University, Taichung, 404, Taiwan.|Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, 404, Taiwan.
authors.forename: Yu-Huei
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Graduate Institute of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, 717, Taiwan.|Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, 717, Taiwan.
authors.forename: Yui-Ping
authors.initials: YP
authors.lastname: Weng
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, 116, Taiwan.
authors.forename: Hsuan-Yuan
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
authors.forename: Sai-Wen
authors.initials: SW
authors.lastname: Tang
authors.affiliation: Graduate Institute of Integrated Medicine, China Medical University, Taichung, 404, Taiwan.
authors.forename: Chao-Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
authors.forename: Chi-Jung
authors.initials: CJ
authors.lastname: Liang
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Ku
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, 116, Taiwan.|Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
authors.forename: Jung-Yaw
authors.initials: JY
authors.lastname: Lin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000071182:Autophagosomes / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D028502:Polygonum / Q000737:chemistry*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology; D000074702:Proteostasis / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000199:Actins; D010936:Plant Extracts; D059808:Polyphenols; D017382:Reactive Oxygen Species