Niclosamide induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes

- Niclosamide showed pro-apoptosis effect on RA FLS but not affected normal FLS.
- Niclosamide-induced apoptosis in RA FLS was achieved via a mitochondrial-dependent pathway.
- Niclosamide regulated the expressions of Bax and Bcl-2 and release of cytochrome C.
- AKT was also required for Niclosamide-induced apoptosis in RA FLS.

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.