title: Bufalin exerts inhibitory effects on IL-1β-mediated proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes.
abstract: Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) proliferate abnormally and resist apoptosis. Bufalin inhibits cell proliferation and induces apoptosis in human cancer cells. In this study, we explored the effects of bufalin on interleukin-1beta (IL-1β)-induced proliferation and apoptosis of RAFLSs. The cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining, respectively. Bufalin dose-dependently inhibited IL-1β-induced RAFLS proliferation. Mechanistically, bufalin decreased the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB), both of which are involved in IL-1β-mediated RAFLS proliferation. Moreover, bufalin induced apoptosis and mitochondrial damage of RAFLSs, which was associated with Bcl-2 downregulation, Bax upregulation, mitochondrial cytochrome c release, and enhanced cleavages of caspase-3 and poly-(ADP-ribose) polymerase. Collectively, our results reveal that bufalin suppresses IL-1β-induced proliferation of RAFLSs through MAPK and NF-κB signaling pathways and induces RAFLS apoptosis via the mitochondria-dependent pathway.
authors.affiliation: Department of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China, springdayspring@sohu.com.
authors.forename: Yue-wen
authors.initials: YW
authors.lastname: Chang
authors.forename: Yong-fang
authors.initials: YF
authors.lastname: Zhao
authors.forename: Yue-long
authors.initials: YL
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.forename: Jian
authors.initials: J
authors.lastname: Pang
authors.forename: Hong-sheng
authors.initials: HS
authors.lastname: Zhan
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002018:Bufanolides / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D002018:Bufanolides; D053583:Interleukin-1beta; C022777:bufalin
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