ALBERT

Description:    The pseudo-tumoral expansion of fibroblast-like synoviocytes is a hallmark of rheumatoid arthritis (RA), and targeting rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) may have therapeutic potentials in this disease. Andrographolide, a diterpenoid compound isolated from the herb Andrographis paniculata , has been reported to have potent anti-inflammatory activity. In the present study, we aimed to investigate the effects of andrographolide on human RAFLSs and the underlying molecular mechanism(s). RAFLSs were isolated from patients with RA and treated with or without various concentrations (i.e., 10, 20, and 30 μM) of andrographolide for 48 h. 3-[4,5-Dimethyl-2-yl]-2,5-diphenyl tetrazolium bromide assay revealed that andrographolide treatment decreased the proliferation of RAFLSs in a dose-dependent manner. Cell cycle analysis using propidium iodide (PI) staining showed a G0/G1 cell cycle arrest in andrographolide-treated RAFLSs. Immunoblotting analysis of key cell cycle regulators demonstrated that andrographolide treatment caused a dose-dependent increase in the expression of cell-cycle inhibitors p21 and p27 and a concomitant reduction of cyclin-dependent kinase 4. Exposure to andrographolide-induced apoptosis of RAFLSs measured by annexin V/PI double staining, which was coupled with promotion of cytochrome C release from mitochondria and activation of caspase-3. Moreover, andrographolide-treated RAFLSs displayed a significant decrease in the Bcl-2/Bax ratio compared to untreated cells. In conclusion, our data demonstrate that andrographolide exerts anti-growth and pro-apoptotic effects on RAFLSs, thus may have therapeutic potential for the treatment of RA. Content Type Journal Article Pages 47-56 DOI 10.1007/s10565-011-9204-8 Authors Jie Yan, Faculty of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Yang Chen, Faculty of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Chao He, Faculty of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Zhen-zhen Yang, Faculty of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Cheng Lü, Faculty of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Xin-shan Chen, Faculty of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Journal Cell Biology and Toxicology Online ISSN 1573-6822 Print ISSN 0742-2091 Journal Volume Volume 28 Journal Issue Volume 28, Number 1