title: Niclosamide induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes.
abstract: To explore the effects of niclosamide on the viability and apoptosis of rheumatoid arthritis of fibroblast-like synoviocytes (rheumatoid arthritis (RA)fibroblast-like synoviocytes (FLS)), FLS obtained from RA patients were treated with niclosamide. Niclosamide significantly inhibited the viability of RA FLS in a concentration-dependent manner. Niclosamide treated FLS showed a significant increase in the percentage of apoptosis and higher intracellular ROS levels. N-acetyl-l-cysteine (NAC) pretreatment significantly attenuated niclosamide-induced apoptosis. The apoptotic response was due to the up-regulation of pro-apoptotic protein, Bax, and down-regulation of antiapoptotic protein, B cell lymphoma 2 (Bcl-2). The activation of mitochondrial pathway in niclosamide-treated RA FLS induced the cytochrome C, cleavage of caspase-9 and caspase-3. Additionally, niclosamide inhibited the phosphorylation of Akt. Collectively, our results reveal that niclosamide inhibits cell proliferation and induces mitochondrial apoptosis of RAFLSs, which is associated with the modulation of Akt signaling pathways.
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Mingcheng
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Hanshi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: lliuq@mail.sysu.edu.cn.
authors.forename: Liuqin
authors.initials: L
authors.lastname: Liang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009534:Niclosamide / Q000008:administration & dosage*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D009534:Niclosamide; D051058:Oncogene Protein v-akt; D053148:Caspase 3; D053453:Caspase 9; D000111:Acetylcysteine
keywords: Apoptosis; Fibroblast-like synoviocytes; Niclosamide