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Anticancer effects of crude extract from Melia toosendan Sieb. et Zucc on hepatocellular carcinoma in vitro and in vivo

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Abstract

Objective

To investigate the anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc and its possible molecular mechanisms in vitro and in vivo.

Methods

Transonic alcohol-chloroform extraction method was used to extract toosendanin from the bark of Melia toosendan Sieb. et Zucc, and the content of toosendanin in the crude extract was measured by high performance liquid chromatography (HPLC). Anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc were investigated in in vivo and in vitro studies. In the in vitro experiment, human hepatocellular carcinoma cell lines SMMC-7721 and Hep3B were co-incubated with toosendanin crude extract of different concentrations, respectively. In the in vivo experiment, BALB/c mice were subcutaneously inoculated with mouse hepatocellular carcinoma H22 cells and treated with crude extract.

Results

HPLC revealed the content of toosendanin was about 15%. Crude extract from Melia toosendan Sieb. et Zucc inhibited cancer cells growth in a dose- and time-dependent manner. The 50% inhibitory concentration (IC50, 72 h) was 0.6 mg/L for SMMC-7721 cells and 0.8 mg/L for Hep3B cells. Both high-dose [0.69 mg/(kg d)] and low-dose [0.138 mg/(kg d)] crude extract could markedly suppress cancer growth, and the inhibition rate was greater than 50%. Hematoxylin and eosin staining showed necrotic area in cancers and transmission electron microscopy displayed necrotic and apoptotic cancer cells with apoptotic bodies. Immunohistochemistry showed that the expression of Bax and Fas increased and the expression of Bcl-2 reduced.

Conclusions

Toosendanin extract has potent anti-cancer effects via suppressing proliferation and inducing apoptosis of cancer cells in vivo and in vitro. The mechanism of apoptosis involves in mitochondrial pathway and death receptor pathway.

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References

  1. Shi YL, Chen WY. Effect of toosendanin on acetylcholine level of rat brain, a microdialysis study. Brain Res 1999;850:173–178.

    Article  CAS  PubMed  Google Scholar 

  2. Tang Y, Guo H, Hu DB, Zhang Ji. A study of ultrasoundassisted extraction of toosendanin with water from bark of melia toosendan sieb. T zucc. J Southwest Univ Natl (Nat Sci Ed, Chin) 2004;30:714–717.

    CAS  Google Scholar 

  3. Jiang P, An XN. Comparative study on extraction methods of toosendanin. Chem Ind Forest Prod (Chin) 2005;25:79–82.

    Google Scholar 

  4. Chung CC, Hsie TH, Chen SF, Liang HT. The structure of Chuanliansu (toosendanin). Acta Chim Sin (Chin) 1975;33:35–47.

    CAS  Google Scholar 

  5. Shu GX, Liang XT. A correction of the structure of Chuanliansu. Acta Chim Sin (Chin) 1980;38:196–198.

    CAS  Google Scholar 

  6. Shi YL, Li MF. Biological effects of toosendanin, a triterpenoid extracted from Chinese traditional medicine. Prog Neurobiol 2007;82:1–10.

    Article  CAS  PubMed  Google Scholar 

  7. Zhou JY, Wang ZF, Ren XM, Tang MZ, Shi YL. Antagonism of botulinum toxin type A-induced cleavage of SNAP-25 in rat cerebral synaptosome by toosendanin. FEBS Lett 2003;555:375–379.

    Article  CAS  PubMed  Google Scholar 

  8. Shi YL, Wang ZF. Cure of experimental botulism and antibotulismic effect of toosendanin. Acta Pharmacol Sin 2004;25:839–848.

    CAS  PubMed  Google Scholar 

  9. Tang MZ, Wang ZF, Shi YL. Involvement of cytochrome c release and caspase activation in toosendanin-induced PC12 cell apoptosis. Toxicology 2004;201:31–38.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang B, Wang ZF, Tang MZ, Shi YL. Growth inhibition and apoptosis-induced effect on human cancer cells of toosendanin, a triterpenoid derivative from Chinese traditional medicine. Invest New Drugs 2005;23:547–553.

    Article  CAS  PubMed  Google Scholar 

  11. Yu JC, Min ZD, LP NY. Melia toosendan regulates PC12 cell differentiation via the activation of protein kinase A and extracellular signal-regulated kinases. Neurosignals 2004;13:248–257.

    Article  PubMed  Google Scholar 

  12. He YJ, Wang J, Liu XL, Zhang L, Yi G, Li CW, et al. Toosendanin inhibits hepatocellular carcinoma cells by inducing mitochondria-dependent apoptosis. Planta Med 2010;76:1–7.

    Article  Google Scholar 

  13. Zhou J, Jia GR, He XY. Pharmacokinetics researches of toosendanin. Chin Herb Med (Chin) 1982;13:24–26.

    Google Scholar 

  14. Li PZ, Shi XC, Xue ZH, Li JF, Sun GZ, Qin BY. Researches on pharmacological and toxicological effects of toosendanin. Chin Herb Med (Chin) 1982;13:29–32.

    CAS  Google Scholar 

  15. Zhang Y, Qi X, Gong L, Li Y, Liu L, Xue X, et al. Roles of reactive oxygen species and MAP kinases in the primary rat hepatocytes death induced by toosendanin. Toxicology 2008;249:62–68.

    Article  CAS  PubMed  Google Scholar 

  16. Uddin SJ, Nahar L, Shilpi JA, Shoeb M, Borkowski T, Gibbons S, et al. Gedunin, a limonoid from Xylocarpus granatum, inhibits the growth of CaCo-2 colon cancer cell line in vitro. Phytother Res 2007;21:757–761.

    Article  CAS  PubMed  Google Scholar 

  17. Tang Y, Liu SM, Hu DB, Guo H, Zhang J, Li F. Determination of toosendain in the bark of melia toosendan sieb. et Zuccc by reversed-phase high performance liquid chromatography. Chem Res Applic (Chin) 2005;17:276–278.

    CAS  Google Scholar 

  18. Zhang XF, Zhang SF. Acute LD50 determination of toosendanin in mice by ip injection. J Tradit Chin Veterin Med (Chin) 2004;3:12–13.

    CAS  Google Scholar 

  19. Peyruchaud O, Serre CM, NicAmhlaoibh R, Fournier P, Clezardin P. Angiostatin inhibits bone metastasis formation in nude mice through a direct anti-osteoclastic activity. J Biol Chem 2003;278:45826–45832.

    Article  CAS  PubMed  Google Scholar 

  20. Jiang P, Ye HL, An XN. Studies on extraction of extractives from Melia azedarach L. and its bacteriostatic activity. Chem Ind Forest Prod 2004;24:23–27.

    CAS  Google Scholar 

  21. Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature 2001;411:342–348.

    Article  CAS  PubMed  Google Scholar 

  22. Cragg GM, Newman DJ, Snader KM. Natural products in drug discovery and development. J Nat Prod 1997;60:52–60.

    Article  CAS  PubMed  Google Scholar 

  23. Debatin, K. Activation of apoptosis pathways by anticancer treatment. Toxicol Lett 2000;112-113:41–48.

    Article  CAS  PubMed  Google Scholar 

  24. Kaufmann SH, Earnshaw WC. Induction of apoptosis by cancer chemotherapy. Exp Cell Res 2000;256:42–49.

    Article  CAS  PubMed  Google Scholar 

  25. Cheng J, Haas M. Frequent mutations in the p53 tumor suppressor gene in human leukemia T-cell lines. Mol Cell Biol 1990;10:5502–5509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, et al. p53 status and the efficacy of cancer therapy in vivo. Science 1994;266:807–810.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, 400016, China

    Xiao-ling Liu  (刘小玲), Hong Wang  (王 虹), Ling Zhang  (张 伶), Jin Wang  (王 进), Peng Wang  (王 鹏), Xiao He  (贺 潇) & Yu-juan He  (何於娟)

  2. Department of Laboratory Medicine, People’s Hospital, Pengzhou, Sichuan Province, 611930, China

    You-liang Wang  (王友良)

Authors
  1. Xiao-ling Liu  (刘小玲)
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  2. Hong Wang  (王 虹)
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  3. Ling Zhang  (张 伶)
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  4. You-liang Wang  (王友良)
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  5. Jin Wang  (王 进)
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  6. Peng Wang  (王 鹏)
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  7. Xiao He  (贺 潇)
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  8. Yu-juan He  (何於娟)
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Corresponding author

Correspondence to Yu-juan He  (何於娟).

Additional information

Supported by the Natural Science Foundation Project of Science Committee of Chongqing, China (No. CQ CSTC 2009BB5258)

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Liu, Xl., Wang, H., Zhang, L. et al. Anticancer effects of crude extract from Melia toosendan Sieb. et Zucc on hepatocellular carcinoma in vitro and in vivo . Chin. J. Integr. Med. 22, 362–369 (2016). https://doi.org/10.1007/s11655-015-2084-7

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  • DOI: https://doi.org/10.1007/s11655-015-2084-7

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