Oxymatrine Extracted from Sophora flavescens Inhibited Cell Growth and Induced Apoptosis in Human Osteosarcoma MG-63 Cells In Vitro

Abstract

Oxymatrine, one of the most active components of the ethanol extracts from Sophora flavescens, is known for its potent antitumor activity both in vitro and in vivo. However, the mechanism of its action in mediating the cell apoptosis remains elusive. In this study, we investigated the proliferation inhibitory and apoptotic activities of oxymatrine against human osteosarcoma MG-63 cells. The compound was found to markedly and dose-dependently inhibit the cell proliferation determined by 5-bromo-2-deoxyuridine incorporation. Oxymatrine also induced the cell apoptosis in a dose- and time-dependent manner as showed by the annexin V-FITC/PI double staining and TUNEL assay. Furthermore, a disruption of mitochondrial membrane potential and an up-regulation of cleaved caspases-3, and-9 and downregulation of Bax/Bcl-2 was evidenced in the oxymatrine-treated cells. These proteins have been known to play a pivotal role in the regulation of apoptosis. In conclusion, these observations indicate of the oxymatrine potential as an effective antitumor agent against osteosarcoma. Moreover, the compound appears to exert its anti-tumor action by stimulating the caspase-triggered signaling pathway.

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References

  1. 1.

    Zhu, L., McManus, M. M., & Hughes, D. P. (2013). Understanding the biology of bone sarcoma from early initiating events through late events in metastasis and disease progression. Frontiers in Oncology, 3, 230.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. 2.

    Ek, E. W., et al. (2011). Surgical options for reconstruction of the extensor mechanism of the knee after limb-sparing sarcoma surgery: An evidence-based review. Archives of Orthopaedic and Trauma Surgery, 131(4), 487–495.

    Article  PubMed  Google Scholar 

  3. 3.

    Broker, L. E., Kruyt, F. A., & Giaccone, G. (2005). Cell death independent of caspases: A review. Clinical Cancer Research, 11(9), 3155–3162.

    Article  PubMed  Google Scholar 

  4. 4.

    Li, X. M., & Brown, L. (2009). Efficacy and mechanisms of action of traditional Chinese medicines for treating asthma and allergy. Journal of Allergy and Clinical Immunology, 123(2), 297–306; quiz 307–308.

  5. 5.

    Chai, N. L., et al. (2012). Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells. World Journal of Gastroenterology, 18(31), 4199–4206.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. 6.

    Guzman, J. R., et al. (2013). Oxymatrine prevents NF-kappaB nuclear translocation and ameliorates acute intestinal inflammation. Scientific Reports, 3, 1629.

    Article  PubMed Central  PubMed  Google Scholar 

  7. 7.

    Cao, Y. G., et al. (2010). Antiarrhythmic effects and ionic mechanisms of oxymatrine from Sophora flavescens. Phytotherapy Research, 24(12), 1844–1849.

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Yang, Y., et al. (2012). Antiviral effect of matrine against human enterovirus 71. Molecules, 17(9), 10370–10376.

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Chen, J., et al. (2006). Effects of Matrine Injection on T-lymphocyte subsets of patients with malignant tumor after gamma knife radiosurgery. Zhong Xi Yi Jie He Xue Bao, 4(1), 78–79.

    Article  PubMed  Google Scholar 

  10. 10.

    Ma, L., et al. (2008). Anticancer effects of the Chinese medicine matrine on murine hepatocellular carcinoma cells. Planta Medica, 74(3), 245–251.

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Dai, Z. J., et al. (2009). Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3. Journal of Ethnopharmacology, 123(1), 91–96.

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Liu, T., et al. (2010). Matrine inhibits proliferation and induces apoptosis of pancreatic cancer cells in vitro and in vivo. Biological and Pharmaceutical Bulletin, 33(10), 1740–1745.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Ek, E. T., & Choong, P. F. (2006). The role of high-dose therapy and autologous stem cell transplantation for pediatric bone and soft tissue sarcomas. Expert Review of Anticancer Therapy, 6(2), 225–237.

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Hail, N., Jr. (2005). Mitochondria: A novel target for the chemoprevention of cancer. Apoptosis, 10(4), 687–705.

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Sun, S. Y., Hail, N., Jr., & Lotan, R. (2004). Apoptosis as a novel target for cancer chemoprevention. Journal of the National Cancer Institute, 96(9), 662–672.

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Yang, C., et al. (2009). RAIDD expression is impaired in multidrug resistant osteosarcoma cell lines. Cancer Chemotherapy and Pharmacology, 64(3), 607–614.

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Luo, C., et al. (2007). Matrine induced gastric cancer MKN45 cells apoptosis via increasing pro-apoptotic molecules of Bcl-2 family. Toxicology, 229(3), 245–252.

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Zhang, L., et al. (2007). Effect of matrine on HeLa cell adhesion and migration. European Journal of Pharmacology, 563(1–3), 69–76.

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Liu, Y., et al. (2014). Anti-tumor activities of matrine and oxymatrine: Literature review. Tumor Biology, 35, 5111–5119.

  20. 20.

    Yan, F., Liu, Y., & Wang, W. (2013). Matrine inhibited the growth of rat osteosarcoma UMR-108 cells by inducing apoptosis in a mitochondrial-caspase-dependent pathway. Tumor Biology, 34(4), 2135–2140.

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Liu, X. Y., et al. (2008). Matrine inhibits invasiveness and metastasis of human malignant melanoma cell line A375 in vitro. International Journal of Dermatology, 47(5), 448–456.

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Zhang, S., et al. (2009). Matrine induces programmed cell death and regulates expression of relevant genes based on PCR array analysis in C6 glioma cells. Molecular Biology Reports, 36(4), 791–799.

    Article  CAS  PubMed  Google Scholar 

  23. 23.

    Kroemer, G., Galluzzi, L., & Brenner, C. (2007). Mitochondrial membrane permeabilization in cell death. Physiological Reviews, 87(1), 99–163.

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Launay, S., et al. (2005). Vital functions for lethal caspases. Oncogene, 24(33), 5137–5148.

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Cavalcanti, B. C., et al. (2012). Involvement of intrinsic mitochondrial pathway in neosergeolide-induced apoptosis of human HL-60 leukemia cells: The role of mitochondrial permeability transition pore and DNA damage. Pharmaceutical Biology, 50(8), 980–993.

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Iannolo, G., et al. (2008). Apoptosis in normal and cancer stem cells. Critical Reviews in Oncology/Hematology, 66(1), 42–51.

    Article  PubMed  Google Scholar 

  27. 27.

    Li, M., et al. (2000). Apoptosis induced by cadmium in human lymphoma U937 cells through Ca2+-calpain and caspase-mitochondria-dependent pathways. Journal of Biological Chemistry, 275(50), 39702–39709.

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    Mohamad, N., et al. (2005). Mitochondrial apoptotic pathways. Biocell, 29(2), 149–161.

    CAS  PubMed  Google Scholar 

  29. 29.

    Yin, X. M. (2000). Signal transduction mediated by Bid, a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways. Cell Research, 10(3), 161–167.

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    Takahashi, A., et al. (2004). Oxidative stress-induced apoptosis is associated with alterations in mitochondrial caspase activity and Bcl-2-dependent alterations in mitochondrial pH (pHm). Brain Research Bulletin, 62(6), 497–504.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Yin Zhu.

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Wei, J., Zhu, Y., Xu, G. et al. Oxymatrine Extracted from Sophora flavescens Inhibited Cell Growth and Induced Apoptosis in Human Osteosarcoma MG-63 Cells In Vitro. Cell Biochem Biophys 70, 1439–1444 (2014). https://doi.org/10.1007/s12013-014-0078-2

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Keywords

  • Oxymatrine
  • Sophora flavescens
  • Apoptosis
  • Osteosarcoma