Abstract
Matrine, one of the main active components of the extracts from the dry roots of Sophora flavescens, has a potent antitumor activity in vitro and in vivo. However, the molecular mechanism of cell apoptosis induced by matrine remains elusive. Here, we investigated the apoptosis in matrine-treated rat osteosarcoma UMR-108 cells. The results showed that matrine could inhibit cell proliferation and induce apoptosis in a dose- and time-dependent manner. Further investigation revealed a disruption of mitochondrial transmembrane potential and an upregulation of reactive oxygen species in matrine-treated cells. By western blot analysis, we found the upregulation of cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, and cleaved caspase-9 and the downregulation of Bax/Bcl-2 with different concentrations of matrine. These protein interactions may play a pivotal role in the regulation of apoptosis. Taken together, these results overall indicate that matrine could be used as an effective antitumor agent in therapy of osteosarcoma targets the caspase-dependent signaling pathway.
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Thompson Jr RC, Cheng EY, Clohisy DR, Perentesis J, Manivel C, Le CT. Clin Orthop Relat Res. 2002;397:240–347.
Arndt CA, Crist WM. N Engl J Med. 1999;341:342–52.
Bacci G, Longhi A, Bertoni F, Bacchini P, Ruggeri P, Versari M, et al. Primary high-grade osteosarcoma: comparison between preadolescent and older patients. J Pediatr Hematol Oncol. 2005;27:129–34.
Yang C, Choy E, Hornicek FJ, Wood KB, Schwab JH, Liu X, et al. Histone deacetylase inhibitor (HDACI) PCI-24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells. Cancer Chemother Pharmacol. 2011;67:439–46.
Wittenburg LA, Bisson L, Rose BJ, Korch C, Thamm DH. The histone deacetylase inhibitor valproic acid sensitizes human and canine osteosarcoma to doxorubicin. Cancer Chemother Pharmacol. 2011;67:83–92.
Liu XS, Jiang J, Jiao XY, Wu YE, Lin JH. Matrine-induced apoptosis in leukemia U937 cells: involvement of caspases activation and MAPK-independent pathways. Planta Med. 2006;72:501–6.
Luo C, Zhu Y, Jiang T, Lu X, Zhang W, Jing Q, et al. Matrine induced gastric cancer MKN45 cells apoptosis via increasing pro-apoptotic molecules of Bcl-2 family. Toxicology. 2007;229:245–52.
Zhang L, Wang T, Wen X, Wei Y, Peng X, Li H, et al. Effect of matrine on HeLa cell adhesion and migration. Eur J Pharmacol. 2007;563:69–76.
Yu P, Liu Q, Liu K, Yagasaki K, Wu E, Zhang G. Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-kappaB signaling. Cytotechnology. 2009;59:219–29.
Han Y, Zhang S, Wu J, Yu K, Zhang Y, Yin L, et al. Matrine induces apoptosis of human multiple myeloma cells via activation of the mitochondrial pathway. Leuk Lymphoma. 2010;51:1337–46.
Chen J, Mei Q, Xu YC, Du J, Wei Y, Xu ZM. Effects of matrine injection on T-lymphocyte subsets of patients with malignant tumor after gamma knife radio surgery. Zhong Xi Yi Jie He Xue Bao. 2006;4:78–9.
Ma L, Wen S, Zhan Y, He Y, Liu X, Jiang J. Anticancer effects of the Chinese medicine matrine on murine hepatocellular carcinoma cells. Planta Med. 2008;74:245–51.
Liu T, Song Y, Chen H, Pan S, Sun X. Matrine inhibits proliferation and induces apoptosis of pancreatic cancer cells in vitro and in vivo. Biol Pharm Bull. 2010;33:1740–5.
Dai ZJ, Gao J, Ji ZZ, Wang XJ, Ren HT, Liu XX, et al. Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3. J Ethnopharmacol. 2009;123:91–6.
Ek ET, Choong PF. The role of high-dose therapy and autologous stem cell transplantation for pediatric bone and soft tissue sarcomas. Expert Rev Anticancer Ther. 2006;6:225–37.
Yang C, Hornicek FJ, Wood KB, Schwab JH, Mankin H, Duan Z. RAIDD expression is impaired in multidrug resistant osteosarcoma cell lines. Cancer Chemother Pharmacol. 2009;64:607–14.
Sun SY, Hail Jr N, Lotan R. Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst. 2004;96:662–72.
Hirsch T, Marzo I, Kroemer G. Role of the mitochondrial permeability transition pore in apoptosis. Biosci Rep. 1997;17:67–76.
Iannolo G, Conticello C, Memeo L, De Maria R. Apoptosis in normal and cancer stem cells. Crit Rev Oncol Hematol. 2008;66:42–51.
Mohamad N, Gutierrez A, Nunez M, Cocca C, Martín G, Cricco G, et al. Mitochondrial apoptotic pathways. Biocell. 2005;29:149–61.
Orrenius S, Gogvadze V, Zhivotovsky B. Mitochondrial oxidative stress: implications for cell death. Annu Rev Pharmacol Toxicol. 2007;47:143–83.
Yin XM. Signal transduction mediated by Bid, a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways. Cell Res. 2000;10:161–7.
Takahashi A, Masuda A, Sun M, Centonze VE, Herman B. Oxidative stress-induced apoptosis is associated with alterations in mitochondrial caspase activity and Bcl-2-dependent alterations in mitochondrial pH (pHm). Brain Res Bull. 2004;62:497–504.
Li M, Kondo T, Zhao QL, Li FJ, Tanabe K, Arai Y, et al. Apoptosis induced by cadmium in human lymphoma U937 cells through Ca2+-calpain and caspase-mitochondria-dependent pathways. J Biol Chem. 2000;275:39702–9.
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The authors are grateful to Dr. Wang (Harbin Veterinary Research Institute, CAAS) for his technical help.
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Yan, F., Liu, Y. & Wang, W. Matrine inhibited the growth of rat osteosarcoma UMR-108 cells by inducing apoptosis in a mitochondrial–caspase-dependent pathway. Tumor Biol. 34, 2135–2140 (2013). https://doi.org/10.1007/s13277-013-0744-9
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DOI: https://doi.org/10.1007/s13277-013-0744-9