Skip to main content
SpringerLink
Log in

Molecular mechanisms of antitumor activity of niclosamide

  • Published:
Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry Aims and scope Submit manuscript

Abstract

The review summarizes literature data on the antitumor activity of niclosamide and its molecular mechanisms. Earlier niclosamide was used for treatment of intestinal parasitic infections. Recent screening of various drugs and chemical compounds, aimed at identifying putative agents with high antitumor activity, revealed that it possesses such activity. Niclosamide not only inhibits such signaling pathways as Wnt/β-cate-nin, mTORC1, Stat3, NF-κB and Notch, but also damages tumor cell mitochondria, inhibits proliferation and induces apoptosis. The effectiveness of niclosamide has been demonstrated in vitro experiments as well as in vivo models using xenotransplantation of human tumors to immunodeficient mice. Niclosamide was active not only against tumor cells but also cancer stem cells. Normal cells are resistant to niclosamide. The accumulated experimental data suggest that niclosamide is a promising pharmacological agent for the treatment of various types of cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mashkovskii, M.D., Lekarstvennyie sredstva. V dvukh chastyakh. Chast’ II. 12 Izdanie (Drug Reference Book in two parts. Part II), 12th ed. Moscow: Meditsina, 1993.

    Google Scholar 

  2. Park, J.P. and Fioravanti, C.F., Parasitol. Res., 2006, vol. 98, pp. 200–206.

    Article  CAS  Google Scholar 

  3. Dai, J.R., Coles, G.C., Wang, W., and Liang, Y.S., Trans. R. Soc. Trop. Med. Hyg., 2010, vol. 104, pp. 304–306.

    Article  CAS  Google Scholar 

  4. Park, S.J., Shin, J.H., Kang, H., Hwang, J.J., and Cho, D.H., BMB Rep., 2011, vol. 44, pp. 517–522.

    Article  CAS  Google Scholar 

  5. Chang, Y.W., Yeh, T.K., Lin, K.T., Chen, W.C., Yao, H.T., Lan, S.J., Wu, Y.S., Hsieh, H.P., Chen, C.M., and Chen, C.T., J. Food Drug Anal., 2006, vol. 14, pp. 329–333.

    CAS  Google Scholar 

  6. Pan, J.X., Ding, K., and Wang, C.Y., Chin. J. Cancer, 2012, vol. 31, pp. 178–184. doi: 10.5732/cjc.011

    Article  Google Scholar 

  7. Shipley, J.L. and Butera, J.N., Exp. Hematol., 2009, vol. 37, pp. 649–658. doi: 10.1016/jexphem. 2009.04.002

    Article  CAS  Google Scholar 

  8. Bonnet, D. and Dick, J.E., Nat. Med., 1997, vol. 3, pp. 730–737.

    Article  CAS  Google Scholar 

  9. Guzman, M.L., Neering, S.J., Upchurch, D., Grimes, B., Howard, D.S., Rizzieri, D.A., Luger, S.M., and Jordan, C.T., Blood, 2001, vol. 98, pp. 2301–2307.

    Article  CAS  Google Scholar 

  10. Jin, Y., Lu, Z., Ding, K., Li, J., Du, X., Chen, C., Sun, X., Wu, Y., Zhou, J., and Pan, J., Cancer Res., 2010, vol. 70, pp. 2516–2527. doi: 10.1158/0008-5472

    Article  CAS  Google Scholar 

  11. Chikara, Sh. and Reindl, K., Transl. Lung Cancer Res., 2013, vol. 2, pp. 449–451. doi: 10.3978/jissn.22186751.2013.10.15

    CAS  Google Scholar 

  12. Musse, A.A., Meloty-Kapella, L., and Weinmaster, G., Semin. Cell Dev Biol., 2012, vol. 23, pp. 429–436. doi: 10.1016/jsemcdb.2012.01.011

    Article  CAS  Google Scholar 

  13. Borggrefe, T. and Liefke, R., Cell Cycle, 2012, vol. 11, no. 2, pp. 264–276.

    Article  CAS  Google Scholar 

  14. Wang, A.M., Ku, H.H., Liang, Y.C., Chen, Y.C., Hwu, Y.M., and Yeh, T.S., J. Cell Biochem., 2009, vol. 106, pp. 682?692. doi: 10.1002/jcb.22065

    Article  CAS  Google Scholar 

  15. Kyle, R.A. and Rajkumar, S.V., Expert Rev. Hematol., 2014, vol. 7, pp. 5–7. doi: 10.1586/17474086.2014.870030

    Article  CAS  Google Scholar 

  16. Kyle, R.A., Leukemia, 2005, vol. 19, pp. 910–912.

    Article  CAS  Google Scholar 

  17. Khanim, F.L., Merrick, B.A., Giles, H.V., Jankute, M., Jackson, J.B., Giles, L.J., Birtwistle, J., Bunce, C.M., and Drayson, M.T., Blood Cancer J., 2011, vol. 1, no. 10, e39. doi: 10.1038/bcj.2011.38.

    Article  CAS  Google Scholar 

  18. Park, J.P. and Fioravanti, C.F., Parasitol. Res., 2006, vol. 98, pp. 200–206.

    Article  CAS  Google Scholar 

  19. Wieland, A., Trageser, D., Gogolok, S., Reinartz, R., Höfer, H., Keller, M., Leinhaas, A., Schelle, R., Normann, S., Klaas, L., Waha, A., Koch, P., Fimmers, R., Pietsch, T., Yachnis, A.T., Pincus, D.W., Steindler, D.A., Brüstle, O., Simon, M., Glas, M., and Scheffler, B., Clin. Cancer Res., 2013, vol. 19, pp. 4124–4136. doi: 10.1158/1078-0432.CCR-122895

    Article  CAS  Google Scholar 

  20. Bengochea, A., de Souza, M.M., Lefranois, L., Le Roux, E., Galy, O., Chemin, I., Kim, M., Wands, J.R., Trepo, C., Hainaut, P., Scoazec, J.Y., Vitvitski, L., and Merle, P., Br. J. Cancer, 2008, vol. 99, pp. 143–150. doi: 10.1038/sjbjc.6604422

    Article  CAS  Google Scholar 

  21. Giakoustidis, A., Giakoustidis, D., Mudan, S., Sklavos, A., and Williams, R., Can. J. Gastroenterol. Hepatol., 2015, vol. 29, pp. 212–221.

    Google Scholar 

  22. Kharaishvili, G., Simkova, D., Makharoblidze, E., Trtkova, K., Kolar, Z., and Bouchal, J., Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Republ., 2011, vol. 155, pp. 11–18.

    Article  CAS  Google Scholar 

  23. Reya, T. and Clevers, H., Nature, 2005, vol. 434, pp. 843–850.

    Article  CAS  Google Scholar 

  24. Luis, T.C., Ichii, M., Brugman, M.H., Kincade, P., and Staal, F.J., Leukemia, 2012, vol. 26, pp. 414–421. doi: 10.1038/leu.2011.387

    Article  CAS  Google Scholar 

  25. Tomizawa, M., Shinozaki, F., Motoyoshi, Y., Sugiyama, T., Yamamoto, S., Sueishi, M., and Yoshida, T., Onco Targets Ther., 2013, vol. 6, pp. 1685–1693. doi: 10.2147/OTT.S50065

    Article  CAS  Google Scholar 

  26. Tchissov, V.I. and Rusakov, I.G., Eksper. Klin. Urologiya, 2010, nos. 2–3, pp. 6–7.

    Google Scholar 

  27. Liu, C., Lou, W., Zhu, Y., Nadiminty, N., Schwartz, C.T., Evans, C.P., and Gao, A.C., Clin. Cancer Res., 2014, vol. 20, pp. 3198–3210. doi: 10.1158/10780432.CCR-13-3296

    Article  CAS  Google Scholar 

  28. Jemal, A., Siegel, R., Xu, J., and Ward, E., CA Cancer J. Clin., 2010, vol. 60, pp. 277–300.

    Article  Google Scholar 

  29. Giles, R.H., van Es, J.H., and Clevers, H., Biochim. Biophys. Acta, 2003, vol. 1653, pp. 1–24.

    CAS  Google Scholar 

  30. Stein, U., Arlt, F., Walther, W., Smith, J., Waldman, T., Harris, E.D., Mertins, S.D., Heizmann, C.W., Allard, D., Birchmeier, W., Schlag, P.M., and Shoemaker, R.H., Gastroenterology, 2006, vol. 131, pp. 1486–1500.

    Article  CAS  Google Scholar 

  31. Osada, T., Chen, M., and Yang, X.Y., Cancer Res., 2011, vol. 71, pp. 4172–4182.

    Article  CAS  Google Scholar 

  32. Chen, M., Wang, J., Lu, J., Bond, M.C., Ren, X.R., Lyerly, H.K., Barak, L.S., and Chen, W., Biochemistry, 2009, vol. 48, pp. 10267–10274. doi: 10.1021/bi9009677

    Article  CAS  Google Scholar 

  33. Kim, J.H., Kim, C.N., Kim, S.Y., Lee, J.S., Cho, D., Kim, J.W., and Yoon, S.Y., Oncol. Rep., 2009, vol. 22, pp. 41–47.

    CAS  Google Scholar 

  34. Sack, U., Walther, W., Scudiero, D., Selby, M., Aumann, J., Lemos, C., Fichtner, I., Schlag, P.M., Shoemaker, R.H., and Stein, U., Mol. Biol. Cell., 2011, vol. 22, pp. 3344–3354. doi: 10.1091/mbc.E10-090739

    Article  CAS  Google Scholar 

  35. Helfman, D.M., Kim, E.J., Lukanidin, E., and Grigorian, M., Br. J. Cancer, 2005, vol. 92, pp. 1955–1958.

    Article  CAS  Google Scholar 

  36. Yoshioka, S., King, M.L., Ran, S., Okuda, H., MacLean, J.A., McAsey, M.E., Sugino, N., Brard, L., Watabe, K., and Hayashi, K., Mol. Cancer Res., 2012, vol. 10, pp. 469–482. doi: 10.1158/15417786

    Article  CAS  Google Scholar 

  37. King, M.L., Lindberg, M.E., Stodden, G.R., Okuda, H., Ebers, S.D., Johnson, A., Montag, A., Lengyel, E., MacLean, J.A. 2nd, and Hayashi, K., Oncogene, 2015, vol. 34, pp. 3452–3462. doi: 10.1038/onc.2014.277

    Article  CAS  Google Scholar 

  38. Arend, R.C., Londoño-Joshi, A.I., Samant, R.S., Li, Y., Conner, M., Hidalgo, B., Alvarez, R.D., Landen, C.N., Straughn, J.M., and Buchsbaum, D.J., Gynecologic Oncology, 2014, vol. 134, pp. 112–120. doi: 10.1016/jygyno.2014.04.005

    Article  CAS  Google Scholar 

  39. Yo, Y.T., Lin, Y.W., Wang, Y.C., Balch, C., Huang, R.L., Chan, M.W., Sytwu, H.K., Chen, C.K., Chang, C.C., Nephew, K.P., Huang, T., Yu, M.H., and Lai, H.C., Mol. Cancer Ther., 2012, vol. 11, pp. 1703–1712. doi: 10.1158/1535-7163.MCT-12-0002

    Article  CAS  Google Scholar 

  40. Marur, S., and Forastiere, A.A., Mayo Clin. Proc., 2008, vol. 83, pp. 489–501. doi: 10.4065/83.4.489

    Article  Google Scholar 

  41. Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Murray, T., et al., CA Cancer J. Clin., 2008, vol. 58, pp. 71–96. doi: 10.3322/CA.2007.0010

    Article  Google Scholar 

  42. Quesnelle, K.M., Wheeler, S.E., Ratay, M.K., and Grandis, J.R., Cancer Biol. Ther., 2012, vol. 13, pp. 935–945. doi: 10.4161/cbt.20846

    Article  CAS  Google Scholar 

  43. Lai, S.Y. and Johnson, F.M., Drug Resist Update, 2010, vol. 13, pp. 67–78. doi: 10.1016/jdrup.2010.04.001

    Article  CAS  Google Scholar 

  44. Inghirami, G., Chiarle, R., Simmons, W.J., Piva, R., Schlessinger, K., and Levy, D.E., Cell Cycle, 2005, vol. 4, pp. 1131–1133.

    Article  CAS  Google Scholar 

  45. Su, F., Ren, F., Rong, Y., Wang, Y., Geng, Y., Wang, Y., Feng, M., Ju, Y., Li, Y., Zhao, Z.J., Meng, K., and Chang, Z., Breast Cancer Res., 2012, vol. 14, R38. doi: 10.1186/bcr3134

    Article  CAS  Google Scholar 

  46. Li, R., You, S., Hu, Z., Chen, Z. G., Sica, G.L., Khuri, F.R., Curran, W.J., Shin, D.M., and Deng, X., PLoS One 2013, vol. 8, e74670. doi: 10.1371/journalpone.0074670

    Article  CAS  Google Scholar 

  47. Li, R., Hu, Z., Sun, S.Y., Chen, Z.G., Owonikoko, T.K., Sica, G.L., Ramalingam, S.S., Curran, W.J., Khuri, F.R., and Deng, X., Mol. Cancer Ther., 2013, vol. 12, pp. 2200–2212. doi: 10.1158/1535-7163.MCT13-0095

    Article  CAS  Google Scholar 

  48. Ye, T., Xiong, Y., Yan, Y., Xia, Y., Song, X., Liu, L., Li, D., Wang, N., Zhang, L., Zhu, Y., Zeng, J., Wei, Y., and Yu, L., PLoS One, 2014, vol. 9, e85887. doi: 10.1371/journalpone.0085887

    Google Scholar 

  49. Wang, Y.C., Chao, T.K., Chang, C.C., Yo, Y.T., Yu, M.H., and Lai, H.C., PLoS One, 2013, vol. 8, e74538. doi: 10.1371/journalpone.0074538

    Article  Google Scholar 

  50. Moskaleva, E.Yu. and Severin S.E., in Biologiya stvolovykh kletok i kletochnye tekhnologii (Stem cell biology and cell technologies), vol. 1, Pal’tsev, M.A., Ed., Moscow: Meditsina, Shiko, 2009, pp. 206–232.

  51. Wilson, B.J., Schatton, T., Frank, M.H., and Frank, N.Y., Curr. Colorectal Cancer Rep., 2011, vol. 7, pp. 128–135.

    Article  Google Scholar 

  52. Frank, N.Y., Schatton, T., and Frank, M.H., J. Clin. Invest., 2010, vol. 120, pp. 41–50. doi: 10.1172/JCI41004

    Article  CAS  Google Scholar 

  53. Bao, B., Ahmad, A., Azmi, A.S., Ali, S., and Sarkar, F.H., Curr. Protoc. Pharmacol.; 2013, Chapter 14, Unit 14.25. doi: 10.1002/0471141755ph1425s61

    Google Scholar 

  54. Kemper, K., Grandela, C., and Medem, J.P., Oncotarget, 2010, vol. 1, no. 6, pp. 387–395.

    Article  Google Scholar 

  55. Pannuti, A., Foreman, K., Rizzo, P., Osipo, C., Golde, T., Osborne, B., and Miele, L., Clin. Cancer Res., 2010, vol. 16, no. 12, pp. 3141–3152. doi: 10.1158/10780432.CCR-09-2823

    Article  CAS  Google Scholar 

  56. Takebe, N., and Ivy, S.P., Clin. Cancer Res., 2010, vol. 16, no. 12, pp. 3106–3112. doi: 10.1158/10780432.CCR-09-2934

    Article  CAS  Google Scholar 

  57. Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., et al., Proc. Natl. Acad. Sci. USA, 2003, vol. 100, pp. 3983–3988.

    Article  CAS  Google Scholar 

  58. Al-Hajj, M. and Clarke, M.F., Oncogene, 2004, vol. 23, pp. 7274–7282.

    Article  CAS  Google Scholar 

  59. Hirschmann-Jax, C., Foster, A.E., Wulf, G.G., Nuchtern, J.G., Jax, T.W., Gobel, U., Goodell, M.A., and Brenner, M.K., Proc. Natl. Acad. Sci. USA, 2004, vol. 101, pp. 14228–14233.

    Article  CAS  Google Scholar 

  60. Gottesman, M.M., Fojo, T., and Bates, S.E., Nat. Rev. Cancer, 2002, vol. 2, pp. 48–58.

    Article  CAS  Google Scholar 

  61. Choi, C.H., Cancer Cell Int., 2005, vol. 4, pp. 5–30.

    Google Scholar 

  62. Baumann, M., Krause, M., and Hill, R., Nat. Rev. Cancer, 2008, vol. 8, pp. 545–554. doi: 10.1038/nrc2419

    Article  CAS  Google Scholar 

  63. Kondrasheva, I.G., Zamulaeva, I.A., Saenko, A.S., Smirnova, S.G., Orlova, N.V., Selivanova, E.I., Moskaleva, E.Yu., and Severin, S.E., Molekul. Med., 2011, vol. 6, pp. 25–32.

    Google Scholar 

  64. Kemper, K., Grandela, C., and Medem, J.P., Oncotarget, 2010, vol. 1, no. 6, pp. 387–395.

    Article  Google Scholar 

  65. Ono, M., Yin, P., Navarro, A., Moravek, M.B., Coon, J.S. 5th, Druschitz, S.A., Serna, V.A., Qiang, W., Brooks, D.C., Malpani, S.S., Ma, J., Ercan, C.M., Mittal, N., Monsivais, D., Dyson, M.T., Yemelyanov, A., Maruyama, T., Chakravarti, D., Kim, J.J., Kurita, T., Gottardi, CJ., and Bulun, S.E., Proc. Natl. Acad. Sci. USA, 2013, vol. 110, pp. 17053–17058. doi: 10.1073/pnas.1313650110

    Article  CAS  Google Scholar 

  66. Ono, M., Yin, P., Navarro, A., Moravek, M.B., Coon, J.S. 5th, Druschitz, S.A., Gottardi, C.J., and Bulun, S.E., Fertil. Steril., 2014, vol. 101, no. 5, pp. 1441–1449. doi: 10.1016/jfertnstert.2014.01.017

    Article  CAS  Google Scholar 

  67. Lee, S.L., Son, A.R., Ahn, J., and Song, J.Y., Biomed. Pharmacother., 2014, vol. 68, no. 5, pp. 619–624. doi: 10.1016/jbiopha.2014.03.018

    Article  CAS  Google Scholar 

  68. Tao, H., Zhang, Y., Zeng, X., Shulman, G.I., and Jin, S., Nat. Med., 2014, vol. 20, pp. 1263–1269 doi: 10.1038/nm.3699

    Article  CAS  Google Scholar 

  69. Meijer, A.J. and Codogno, P., Int. J. Biochem. Cell Biol., 2004, vol. 36, pp. 2445–2462.

    Article  CAS  Google Scholar 

  70. Xie, Z., Nair, U., and Klionsky, D.J., Mol. Biol. Cell., 2008, vol. 19, pp. 3290–3298. doi: 10.1091/mbc.E0712-1292

    Article  CAS  Google Scholar 

  71. Balgi, A.D., Fonseca, B.D., Donohue, E., Tsang, T.C., Lajoie, P., Proud, C.G., Nabi, I.R., and Roberge, M., PLoS One, 2009, vol. 4, e7124. doi: 10.1371/journalpone.0007124

    Article  Google Scholar 

  72. Fonseca, B.D., Diering, G.H., Bidinosti, M.A., Dalal, K., Alain, T., Balgi, A.D., Forestieri, R., Nodwell, M., Rajadurai, C.V., Gunaratnam, C., Tee, A.R., Duong, F., Andersen, R.J., Orlowski, J., Numata, M., Sonenberg, N., and Roberge, M.J., J. Biol. Chem., 2012, vol. 287, no. 21, pp. 17530–17545. doi: 10.1074/jbc.M112.359638

    Article  CAS  Google Scholar 

  73. Chen, H., Yang, Z., Ding, C., Chu, L., Zhang, Y., Terry, K., Liu, H., Shen, Q., and Zhou, J., ACS Med. Chem. Lett., 2013, vol. 4, no. 2, pp. 180–185.

    Article  Google Scholar 

  74. Bai, M.-Y. and Yang, H.-Ch., Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2013, vol. 419, pp. 248–256.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Research Centre “Kurchatov Institute”, NBICS-Centre, pl. Akad. Kurchatova 1, Moscow, 123182, Russia

    E. Yu. Moskaleva, V. G. Perevozchikova, A. S. Zhirnik & S. E. Severin

Authors
  1. E. Yu. Moskaleva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. G. Perevozchikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. S. Zhirnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. E. Severin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Yu. Moskaleva.

Additional information

Original Russian Text © E.Yu. Moskaleva, V.G. Perevozchikova, A.S. Zhirnik, S.E. Severin, 2015, published in Biomeditsinskaya Khimiya.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moskaleva, E.Y., Perevozchikova, V.G., Zhirnik, A.S. et al. Molecular mechanisms of antitumor activity of niclosamide. Biochem. Moscow Suppl. Ser. B 9, 312–324 (2015). https://doi.org/10.1134/S1990750815040022

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990750815040022

Keywords

Search

Navigation