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Article

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

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

    Affiliations: Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China, Department of Grass Science, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China, Department of Gynaecology and Obstetrics, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang 163316, P.R. China, Department of Food Science and Engineering, College of Food Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China
  • Pages: 1067-1075
    |
    Published online on: December 3, 2018
       https://doi.org/10.3892/ijmm.2018.4012
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Sun HN, Luo YH, Meng LQ, Piao XJ, Wang Y, Wang JR, Wang H, Zhang Y, Li JQ, Xu WT, Xu WT, et al: Cryptotanshinone induces reactive oxygen species‑mediated apoptosis in human rheumatoid arthritis fibroblast‑like synoviocytes. Int J Mol Med 43: 1067-1075, 2019.
APA
Sun, H., Luo, Y., Meng, L., Piao, X., Wang, Y., Wang, J. ... Jin, C. (2019). Cryptotanshinone induces reactive oxygen species‑mediated apoptosis in human rheumatoid arthritis fibroblast‑like synoviocytes. International Journal of Molecular Medicine, 43, 1067-1075. https://doi.org/10.3892/ijmm.2018.4012
MLA
Sun, H., Luo, Y., Meng, L., Piao, X., Wang, Y., Wang, J., Wang, H., Zhang, Y., Li, J., Xu, W., Liu, Y., Zhang, Y., Zhang, T., Han, Y., Jin, M., Shen, G., Zang, Y., Cao, L., Zhang, D., Jin, C."Cryptotanshinone induces reactive oxygen species‑mediated apoptosis in human rheumatoid arthritis fibroblast‑like synoviocytes". International Journal of Molecular Medicine 43.2 (2019): 1067-1075.
Chicago
Sun, H., Luo, Y., Meng, L., Piao, X., Wang, Y., Wang, J., Wang, H., Zhang, Y., Li, J., Xu, W., Liu, Y., Zhang, Y., Zhang, T., Han, Y., Jin, M., Shen, G., Zang, Y., Cao, L., Zhang, D., Jin, C."Cryptotanshinone induces reactive oxygen species‑mediated apoptosis in human rheumatoid arthritis fibroblast‑like synoviocytes". International Journal of Molecular Medicine 43, no. 2 (2019): 1067-1075. https://doi.org/10.3892/ijmm.2018.4012
Copy and paste a formatted citation
x
Spandidos Publications style
Sun HN, Luo YH, Meng LQ, Piao XJ, Wang Y, Wang JR, Wang H, Zhang Y, Li JQ, Xu WT, Xu WT, et al: Cryptotanshinone induces reactive oxygen species‑mediated apoptosis in human rheumatoid arthritis fibroblast‑like synoviocytes. Int J Mol Med 43: 1067-1075, 2019.
APA
Sun, H., Luo, Y., Meng, L., Piao, X., Wang, Y., Wang, J. ... Jin, C. (2019). Cryptotanshinone induces reactive oxygen species‑mediated apoptosis in human rheumatoid arthritis fibroblast‑like synoviocytes. International Journal of Molecular Medicine, 43, 1067-1075. https://doi.org/10.3892/ijmm.2018.4012
MLA
Sun, H., Luo, Y., Meng, L., Piao, X., Wang, Y., Wang, J., Wang, H., Zhang, Y., Li, J., Xu, W., Liu, Y., Zhang, Y., Zhang, T., Han, Y., Jin, M., Shen, G., Zang, Y., Cao, L., Zhang, D., Jin, C."Cryptotanshinone induces reactive oxygen species‑mediated apoptosis in human rheumatoid arthritis fibroblast‑like synoviocytes". International Journal of Molecular Medicine 43.2 (2019): 1067-1075.
Chicago
Sun, H., Luo, Y., Meng, L., Piao, X., Wang, Y., Wang, J., Wang, H., Zhang, Y., Li, J., Xu, W., Liu, Y., Zhang, Y., Zhang, T., Han, Y., Jin, M., Shen, G., Zang, Y., Cao, L., Zhang, D., Jin, C."Cryptotanshinone induces reactive oxygen species‑mediated apoptosis in human rheumatoid arthritis fibroblast‑like synoviocytes". International Journal of Molecular Medicine 43, no. 2 (2019): 1067-1075. https://doi.org/10.3892/ijmm.2018.4012
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