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Celastrol induced DNA damage, cell cycle arrest, and apoptosis in human rheumatoid fibroblast-like synovial cells
Xu Z.; Wu G.; Wei X.; Chen X.; Wang Y.; Chen L.
2013
Source PublicationAmerican Journal of Chinese Medicine
Volume41Issue:3Pages:615
Abstract

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. © 2013 World Scientific Publishing Company & Institute for Advanced Research in Asian Science and Medicine.

KeywordApoptosis Celastrol Dna Damage Rheumatoid Fibroblast-like Synoviocytes
DOI10.1142/S0192415X13500432
URLView the original
Indexed BySCI
Language英语
WOS Research AreaIntegrative & Complementary Medicine ; General & Internal Medicine
WOS SubjectIntegrative & Complementary Medicine ; Medicine, General & Internal
WOS IDWOS:000319872800011
The Source to ArticleScopus
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Cited Times [WOS]:22   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Av. Padre Tomas Pereira S.J., Taipa, Macau
Recommended Citation
GB/T 7714
Xu Z.,Wu G.,Wei X.,et al. Celastrol induced DNA damage, cell cycle arrest, and apoptosis in human rheumatoid fibroblast-like synovial cells[J]. American Journal of Chinese Medicine,2013,41(3):615.
APA Xu Z.,Wu G.,Wei X.,Chen X.,Wang Y.,&Chen L..(2013).Celastrol induced DNA damage, cell cycle arrest, and apoptosis in human rheumatoid fibroblast-like synovial cells.American Journal of Chinese Medicine,41(3),615.
MLA Xu Z.,et al."Celastrol induced DNA damage, cell cycle arrest, and apoptosis in human rheumatoid fibroblast-like synovial cells".American Journal of Chinese Medicine 41.3(2013):615.
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