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Chinese Journal of Integrative Medicine

, Volume 25, Issue 11, pp 873–878 | Cite as

Mechanism Underlying Antitumor Effects of Sinomenine

  • Le-nyu Gao
  • Bing Zhong
  • Yong WangEmail author
Review

Abstract

Sinomenine (SIN) is a bioactive alkaloid compound extracted from a Chinese medicinal plant Sinomenium acutum. It is a multitarget antitumor natural substance. Various mechanisms have been proposed for the antitumor effects of SIN, such as direct cytotoxicity, induction of apoptosis, sensitization attenuating radiotherapy and chemotherapy, reversal of drug resistance, resistance to distant metastasis, and antiangiogenesis. SIN can be used as a tumor cell killer and an adjuvant to radiotherapy and chemotherapy. However, recent studies are mostly limited to the basic experimental stage; no systematic clinical studies have yet been reported. Therefore, this paper aimed to review the mechanism underlying the antitumor effects of SIN by consulting relevant domestic and foreign studies and to provide a relevant reference for further development, use, and exploration of SIN.

Keywords

antitumor mechanism pharmacology sinomenine Chinese medicine 

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References

  1. 1.
    Zhu Q, Sun YH, Mao L, Liu CP, Jiang B, Zhang W, et al. Antinociceptive effects of sinomenine in a rat model of postoperative pain. Br J Pharmacol 2016;173:1693–1702.CrossRefGoogle Scholar
  2. 2.
    Zhu Q, Sun YH, Zhu J, Fang T, Zhang W, Li JX. Antinociceptive effects of sinomenine in a rat model of neuropathic pain. Sci Rep 2014;4:7270.CrossRefGoogle Scholar
  3. 3.
    Wang Y, Fang YF, Huang WH, Zhou X, Wang MH, Zhong B, et al. Effect of sinomenine on cytokine expression of macrophages and synoviocytes in adjuvant arthritis rats. J Ethnopharmacol 2005;98:37–43.CrossRefGoogle Scholar
  4. 4.
    Cheng Y, Zhang J, Hou W, Wand D, Li F, Zhang Y, et al. Immunoregulatory effects of sinomenine on the T-bet/GATA-3 ratio and Th1/Th2 cytokine balance in the treatment of mesangial proliferative nephritis. Int Immunopharmacol 2009;9:8940–8949.CrossRefGoogle Scholar
  5. 5.
    Jiang YM, Wang DQ. Research progress on antitumor mechanisms of sinomenine. Drugs Clin (Chin) 2016;31:1866–1870.Google Scholar
  6. 6.
    Yang H, Yin P, Shi Z, Ma YC, Zhao CG, Zheng J, et al. Sinomenine, a COX-2 inhibitor, induces cell cycle arrest and inhibits growth of human colon carcinoma cells in vitro and in vivo. Oncol Lett 2006;11:411–418.CrossRefGoogle Scholar
  7. 7.
    Lv Y, Li C, Li S, Hao Z. Sinomenine inhibits proliferation of SGC-7901 gastric adenocarcinoma cells via suppression of cyclooxygenase-2 expression. Oncol Lett 2011;2:741–745.CrossRefGoogle Scholar
  8. 8.
    Jiang Y, Jiao Y, Wang Z, Li T, Liu Y, Li Y, et al. Sinomenine hydrochloride inhibits human glioblastoma cell growth through reactive oxygen species generation and autophagylysosome pathway activation: an in vitro and in vivo study. Int J Mol Sci 2017;18:E1945.CrossRefGoogle Scholar
  9. 9.
    Li X, Wang K, Ren Y, Zhang L, Tang XJ, Zhang HM, et al. MAPK signaling mediates sinomenine hydrochlorideinduced human breast cancer cell death via both reactive oxygen species-dependent and -independent pathways: an in vitro and in vivo study. Cell Death Dis 2014;31:e1356.CrossRefGoogle Scholar
  10. 10.
    Lu XL, Zeng J, Chen YL, He PM, Wen MX, Ren MD, et al. Sinomenine hydrochloride inhibits human hepatocellular carcinoma cell growth in vitro and in vivo: involvement of cell cycle arrest and apoptosis induction. Int J Oncol 2013;42:229–238.CrossRefGoogle Scholar
  11. 11.
    Jiang T, Zhou L, Zhang W, Qu D, Xu X, Yang Y, Li S. Effects of sinomenine on proliferation and apoptosis in human lung cancer cell line NCI-H460 in vitro. Mol Med Rep 2010;3:51–56.PubMedGoogle Scholar
  12. 12.
    Zhou L, Luan H, Liu Q, Jiang T, Liang H, Dong X, et al. Activation of PI3K/Akt and ERK signaling pathways antagonized sinomenine-induced lung cancer cell apoptosis. Mol Med Rep 2012;5:1256–1260.CrossRefGoogle Scholar
  13. 13.
    Deng F, Ma YX, Liang L, Zhang P, Feng J. The proapoptosis effect of sinomenine in renal carcinoma via inducing autophagy through inactivating PI3K/AKT/mTOR pathway. J Biomed Pharmacother 2018;97:1269–1274.CrossRefGoogle Scholar
  14. 14.
    Zhang JX, Yang ZR, Wu DD, Song J, Guo XF, Wang J, et al. Suppressive effect of sinomenine combined with 5-fl uorouracil on colon carcinoma cell growth. Asian Pac J Cancer Prev 2014;15:6737–6743.CrossRefGoogle Scholar
  15. 15.
    Wang J, Yang ZR, Dong WG, Zhang JX, Guo XF, Song J, et al. Cooperative inhibitory effect of sinomenine combined with 5-fluorouracil on esophageal carcinoma. World J Gastroenterol 2013;19:8292–8300.CrossRefGoogle Scholar
  16. 16.
    Liao F, Yang Z, Lu X, Guo X, Dong W. Sinomenine sensitizes gastric cancer cells to 5-fl uorouracil in vitro and in vivo. Oncol Lett 2013;6:1604–1610.CrossRefGoogle Scholar
  17. 17.
    Fu S, Jin L, Gong T, Pan S, Zheng S, Zhang X, et al. Effect of sinomenine hydrochloride on radiosensitivity of esophageal squamous cell carcinoma cells. Oncol Rep 2018;39:1601–1608.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Liu Z, Duan ZJ, Chang JY, Zhang ZF, Chu R, Li YL, et al. Sinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to doxorubicin by downregulation of MDR-1 expression. PLoS One 2014;9:e98560.CrossRefGoogle Scholar
  19. 19.
    Chen Y, Zhang L, Lu X, Wu K, Zeng J, Gao Y, et al. Sinomenine reverses multidrug resistance in bladder cancer cells via P-glycoprotein-dependent and independent manners. Pharmazie 2014;69:48–54.PubMedGoogle Scholar
  20. 20.
    Xie T, Ren HY, Lin HQ, Mao JP, Zhu T, Wang SD, et al. Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway. Int J Oncol 2016;48:2098–2112.CrossRefGoogle Scholar
  21. 21.
    Song L, Liu D, Zhao Y, He J, Kang H, Dai Z, et al. Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-?B activation mediated by IL-4/miR-324-5p/CUEDC2 axis. Biochem Biophys Res Commun 2015;464:705–710.CrossRefGoogle Scholar
  22. 22.
    Song L, Liu D, Zhao Y, He J, Kang H, Dai Z, et al. Sinomenine reduces growth and metastasis of breast cancer cells and improves the survival of tumor-bearing mice through suppressing the SHh pathway. Biomed Pharmacother 2018;98:687–693.CrossRefGoogle Scholar
  23. 23.
    Jiang Y, Jiao Y, Liu Y, Zhang M, Wang Z, Li Y, et al. Sinomenine hydrochloride inhibits the metastasis of human glioblastoma cells by suppressing the expression of matrix metalloproteinase-2/-9 and reversing the endogenous and exogenous epithelial-mesenchymal transition. Int J Mol Sci 2018;19:E844.CrossRefGoogle Scholar
  24. 24.
    Li X, Li P, Liu C, Ren Y, Tang X, Wang K, He J. Sinomenine hydrochloride inhibits breast cancer metastasis by attenuating inflammation-related epithelial-mesenchymal transition and cancer stemness. Oncotarget 2017;8:13560–13574.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Zhao B, Liu L, Mao J, Liu K, Fan W, Liu J, Zhang Z, Li Q. Sinomenine hydrochloride attenuates the proliferation, migration, invasiveness, angiogenesis and epithelialmesenchymal transition of clear-cell renal cell carcinoma cells via targeting Smad in vitro. Biomed Pharmacother 2017;96:1036–1044.CrossRefGoogle Scholar
  26. 26.
    Crawford Y, Ferrara N. VEGF inhibition: insights from preclinical and clinical studies. Cell Tissue Res 2009;335:261–269.CrossRefGoogle Scholar
  27. 27.
    Ferrara N. Pathways mediating VEGF-independent tumor angiogenesis. Cytokine Growth Factor Rev 2010;21:21–26.CrossRefGoogle Scholar
  28. 28.
    Shang B, Cao Z, Zhou Q. Progress in tumor vascular normalization for anticancer therapy: challenges and perspectives. Front Med 2012;6:67–78.CrossRefGoogle Scholar
  29. 29.
    Kok TW, Yue PY, Mak NK, Fan TP, Liu L, Wong RN. The anti-angiogenic effect of sinomenine. Angiogenesis 2005;8:3–12.CrossRefGoogle Scholar
  30. 30.
    Zhang H, Ren Y, Tang X, Wang K, Liu Y, Zhang L, et al. Vascular normalization induced by sinomenine hydrochloride results in suppressed mammary tumor growth and metastasis. Sci Rep 2015;5:8888.CrossRefGoogle Scholar
  31. 31.
    Xie T, Ren HY, Lin HQ, Mao JP, Zhu T, Wang SD, et al. Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway. Int J Oncol 2016;48:2098–2112.CrossRefGoogle Scholar
  32. 32.
    Zhu Q, Sun Y, Mao L, Liu C, Jiang B, Zhang W, et al. Antinociceptive effects of sinomenine in a rat model of postoperative pain. Br J Pharmacol 2016;173:1693–1702.CrossRefGoogle Scholar
  33. 33.
    Fang M, Li J, Zhu D, Luo C, Li C, Zhu C, et al. Effect of sinomenine on the morphine-dependence and related neural mechanisms in mice. Neurochem Res 2017;42:3587–3596.CrossRefGoogle Scholar

Copyright information

© The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Traditional Chinese Medicine, Southwest Hospitalthe Third Military Medical University (Army Military Medical University)ChongqingChina

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