Details

Autor(en) / Beteiligte

• Sun, Hu-Nan
• Luo, Ying-Hua
• Meng, Ling-Qi
• Piao, Xian-Ji
• Wang, Yue
• Wang, Jia-Ru
• Wang, Hao
• Zhang, Yi
• Li, Jin-Qian
• Xu, Wan-Ting
• Liu, Yang
• Zhang, Yu
• Zhang, Tong
• Han, Ying-Hao
• Jin, Mei-Hua
• Shen, Gui-Nan
• Zang, Yan-Qing
• Cao, Long-Kui
• Zhang, Dong-Jie
• Jin, Cheng-Hao

Titel

Cryptotanshinone induces reactive oxygen species‑mediated apoptosis in human rheumatoid arthritis fibroblast‑like synoviocytes

Ist Teil von

• International journal of molecular medicine, 2019-02, Vol.43 (2), p.1067

Ort / Verlag

Athens: Spandidos Publications

Erscheinungsjahr

2019

Quelle

EZB*

Beschreibungen/Notizen

• The present study investigated the mechanisms of apoptosis induced by cryptotanshinone (CT) in human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Cell Counting kit-8 assay was performed to determine the cytotoxic effects of CT in human RA-FLSs, including primary RA-FLS, HFLS-RA and MH7A cells, and in HFLS cells derived from normal synovial tissue. Annexin V-FITC/PI staining was used to detect the apoptotic effects of CT in HFLS-RA and MH7A cells. Flow cytometry was performed to detect the apoptotic and reactive oxygen species (ROS) levels induced by CT in HFLS-RA cells. Western blotting was used to assess the expression levels of proteins associated with apoptosis and with the mitogen-activated protein kinase (MAPK), protein kinase B (Akt), and signal transducer and activator of transcription-3 (STAT3) signaling pathways. The results demonstrated that CT treatment significantly suppressed HFLS-RA and MH7A cell growth, whereas no clear inhibitory effect was observed in normal HFLS cells. CT exposure downregulated the expression levels of B-cell lymphoma 2 (Bcl-2), p-Akt, p-extracellular signal-related kinase and p-STAT3, while it upregulated the expression levels of Bcl-2-associated death promoter (Bad), caspase-3, poly (ADP-ribose) polymerase (PARP), p-p38 and p-c-Jun N-terminal kinase. Following ROS scavenging, the CT-induced apoptosis and altered expression levels of Bcl-2, Bad, cleaved caspase-3 and cleaved PARP were restored. Furthermore, the Akt, MAPK and STAT3 signaling pathways were regulated by intracellular ROS. These results suggest that ROS-mediated Akt, MAPK and STAT3 signaling pathways serve important roles in the CT-induced apoptosis of RA-FLSs.