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Liu H.,97th Hospital of Peoples Liberation Army | Yang Y.,97th Hospital of Peoples Liberation Army | Cai X.,97th Hospital of Peoples Liberation Army | Gao Y.,97th Hospital of Peoples Liberation Army | And 2 more authors.
Pharmaceutical Biology | Year: 2015

Context: Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) play an important role in the initiation and progression of RA, which are resistant to apoptosis and proliferate in an anchorage-independent manner. Objective: The effects of arctigenin on the proliferation and apoptosis of RAFLSs were explored. Materials and methods: Arctigenin (0-160 μM) was used to treat RAFLSs for 48 h. Cell viability and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining. Western blot analysis was performed to detect the changes in apoptosis-related genes. Results and discussion: Arctigenin decreased cell viability by 23, 30, and 38% at the dose of 10, 20, and 30 μM, respectively. The half maximal inhibitory concentration (IC50) of arctignein on RAFLSs was about 38 μM. Moreover, 9, 15, and 21% of RAFLSs are induced apoptosis by 10, 20, and 30 μM of arctigenin. The apoptotic response was due to the loss of mitochondrial membrane potential, coupled with the release of cytochrome C into cytoplasm, 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 arctigenin-treated RAFLSs induced the cleavage of caspase-9, caspase-3, and poly (ADP-ribose) polymerase (PARP). Additionally, arctigenin inhibited the nuclear translocation of p65, decreased the degradation of inhibitor of kappa B alpha (IκBα), and attenuated the phosphorylation of Akt. Conclusion: Our results reveal that arctigenin inhibits cell proliferation and induces mitochondrial apoptosis of RAFLSs, which is associated with the modulation of NF-κB and Akt signaling pathways. © 2015 Informa Healthcare USA, Inc. All rights reserved.

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