期刊
AMERICAN JOURNAL OF CHINESE MEDICINE
卷 41, 期 3, 页码 615-628出版社
WORLD SCIENTIFIC PUBL CO PTE LTD
DOI: 10.1142/S0192415X13500432
关键词
Rheumatoid Fibroblast-Like Synoviocytes; Apoptosis; Celastrol; DNA Damage
资金
- Natural Project of Fujian Province Science and Technology Agency [2009Y2001-1-1]
- Macao Science and Technology Development Fund [077/2011/A3, 074/2012/A3, 045/2011/A]
Celastrol is one of the principal active ingredients of Tripterygium wilfordii Hook. f., a toxic Chinese medical herb traditionally prescribed for controlling pain and inhibiting inflammation in various chronic inflammatory diseases, including rheumatoid arthritis ( RA). Resistance to apoptosis of fibroblast-like synoviocytes is considered a major characteristic of RA. In this study, we test celastrol's cytotoxic effect and potential mechanisms in human rheumatoid synovial fibroblasts (RA-FLS). In the cytotoxic assay, we found that celastrol dose-dependently decreased RA-FLS viability and increased LDH release. The apoptotic nuclear morphology was observed after celastrol treatment as determined by DAPI fluorescence staining. Flow cytometry analysis with PI and Annexin V revealed that celastrol induced RA-FLS cell cycle arrest in the G2/M phase and apoptosis. Furthermore, celastrol dramatically increased expression of Bax/Bcl-2, proteolytic cleavage of Caspase-3, -9, PARP, and decreased expression of FasR. In addition, celastrol treatment resulted in DNA damage. Collectively, we concluded that celastrol inhibits RA-FLS proliferation by inducing DNA damage, cell cycle arrest, and apoptosis in vitro, which might provide data for its application in RA treatment.
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