Skip to main content

Advertisement

SpringerLink
Log in

Cytotoxic and Antitumor Activity of Liposomal Silibinin

  • Published:
BioNanoScience Aims and scope Submit manuscript

Abstract

The cytotoxic and antitumor effect of liposomal form of silibinin was studied. It was shown that the liposomal silibinin reveals more pronounced cytotoxic activity in vitro against HeLa (cervix carcinoma), HT1080 (fibrosarcoma), and MCF-7 (breast adenocarcinoma) human tumor cell lines compared with non-liposomal silibinin. In vivo experiments demonstrated a possibility of parenteral use of the liposomal form. It was demonstrated that intravenous administration of liposomal silibinin has a significant antitumor effect in vivo against murine adenocarcinoma of Ca 755 and leads to inhibition of tumor growth (53.6%) and an increase (49.4%) in the mean life span of experimental animals compared to untreated control and animals receiving non-liposomal forms (free silibinin and its mixture with lecithin) administered orally.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Parveen, A., Akash, M. S., Rehman, K., & Kyunn, W. W. (2016). Anticancer activities of medicinal plants: modulation of p53 expression and induction of apoptosis. Critical Reviews in Eukaryotic Gene Expression, 26, 257–271. https://doi.org/10.1615/CritRevEukaryotGeneExpr.2016016683.

    Article  Google Scholar 

  2. Greenwell, M., & Rahman, P. K. (2015). Medicinal plants: their use in anticancer treatment. Int J Pharm Sci Res, 6, 4103–4112. https://doi.org/10.13040/IJPSR.0975-8232.6(10).4103-12.

    Article  Google Scholar 

  3. Ramasamy, K., & Agarwal, R. (2008). Multitargeted therapy of cancer by silymarin. Cancer Letters, 269(2), 352–362. https://doi.org/10.1016/j.canlet.2008.03.053.

    Article  Google Scholar 

  4. Pradhan, S. C., & Girish, C. (2006). Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. The Indian Journal of Medical Research, 124(5), 491–504.

    Google Scholar 

  5. Zhao, W., Yang, G., Zhong, F., Yang, N., Zhao, X., Qi, Y., & Fan, G. (2014). Isolation and purification of diastereoisomeric flavonolignans from silymarin by binary-column recycling preparative high-performance liquid chromatography. Journal of Separation Science, 37(17), 2300–2306. https://doi.org/10.1002/jssc.201400270.

    Article  Google Scholar 

  6. Kroll, D. J., Shaw, H. S., & Oberlies, N. H. (2007). Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integrative Cancer Therapies, 6(2), 110–119. https://doi.org/10.1177/1534735407301825.

    Article  Google Scholar 

  7. Šimánek, V., Kren, V., Ulrichova, J., Vicar, J., & Cvak, L. (2000). Silymarin: what is in the name...? An appeal for a change of editorial policy. Hepatology, 32(2), 442–444. https://doi.org/10.1053/jhep.2000.9770.

    Article  Google Scholar 

  8. Féher, J., & Lengyel, G. (2012). Silymarin in the prevention and treatment of liver diseases and primary liver cancer. Current Pharmaceutical Biotechnology, 13, 210–217. https://doi.org/10.2174/138920112798868818.

    Article  Google Scholar 

  9. Zhu, X. X., Ding, Y. H., Wu, Y., Qian, L. Y., Zou, H., & He, Q. (2016). Silibinin: a potential old drug for cancer therapy. Expert Review of Clinical Pharmacology, 18, 1–8. https://doi.org/10.1080/17512433.2016.1208563.

    Article  Google Scholar 

  10. Mateen, S., Raina, K., & Agarwal, R. (2013). Chemopreventive and anti-cancer efficacy of silibinin against growth and progression of lung cancer. Nutrition and Cancer, 65, 3–11. https://doi.org/10.1080/01635581.2013.785004.

    Article  Google Scholar 

  11. Khan, A. Q., Khan, R., Tahir, M., Rehman, M. U., Lateef, A., Ali, F., Hamiza, O. O., Hasan, S. K., & Sultana, S. (2014). Silibinin inhibits tumor promotional triggers and tumorigenesis against chemically induced two-stage skin carcinogenesis in Swiss albino mice: possible role of oxidative stress and inflammation. Nutrition and Cancer, 66(2), 249–258. https://doi.org/10.1080/01635581.2014.863365.

    Article  Google Scholar 

  12. Tyagi, A., Agarwal, C., Dwyer-Nield, L. D., Singh, R. P., Malkinson, A. M., & Agarwal, R. (2012). Silibinin modulates TNF-α and IFN-γ mediated signaling to regulate COX2 and iNOS expression in tumorigenic mouse lung epithelial LM2 cells. Molecular Carcinogenesis, 51, 832–842. https://doi.org/10.1002/mc.20851.

    Article  Google Scholar 

  13. Fan, L., Ma, Y., Liu, Y., Li, Q., Chen, J., Dong, Y., & Shi, W. (2014). Silymarin induces cell cycle arrest and apoptosis in ovarian cancer cells. European Journal of Pharmacology, 743, 79–88. https://doi.org/10.1016/j.ejphar.2014.09.019.

    Article  Google Scholar 

  14. Zhang, Y., Ge, Y., Chen, Y., Li, Q., Chen, J., Dong, Y., & Shi, W. (2012). Cellular and molecular mechanisms of silibinin induces cell-cycle arrest and apoptosis on HeLa cells. Cell Biochemistry and Function, 30, 243–248. https://doi.org/10.1002/cbf.1842.

    Article  Google Scholar 

  15. Singh, R. P., Dhanalakshmi, S., Agarwal, C., & Agarwal, R. (2005). Silibinin strongly inhibits growth and survival of human endothelial cells via cell cycle arrest and downregulation of survivin, Akt and NF-kappaB: implications for angioprevention and antiangiogenic therapy. Oncogene, 24, 1188–1202. https://doi.org/10.1038/sj.onc.1208276.

    Article  Google Scholar 

  16. Woo, J. S. (2007). Formulation and biopharmaceutical evaluation of silymarin using SMEDDS. Archives of Pharmacal Research, 30(1), 82–89.

    Article  Google Scholar 

  17. Romanucci, V., Gravante, R., Cimafonte, M., Marino, C. D., Mailhot, G., Brigante, M., Zarrelli, A., & Fabio, G. D. (2017). Phosphate-linked silibinin dimers (PLSd): new promising modified metabolites. Molecules, 22(8), E1323. https://doi.org/10.3390/molecules22081323.

    Article  Google Scholar 

  18. Bijak, M. (2017). Silybin, a major bioactive component of milk thistle (Silybum marianum L. Gaernt.) – chemistry, bioavailability, and metabolism. Molecules, 22(11), E1942. https://doi.org/10.3390/molecules22111942.

    Article  Google Scholar 

  19. Lutsenko, S. V., Gromovykh, T. I., Krasnyuk Jr., I. I., Vasilenko, I. A., & Feldman, N. В. (2018). Antihepatotoxic activity of liposomal silibinin. BioNanoScience, 8(2), 581–586. https://doi.org/10.1007/s12668-018-0512-9.

    Article  Google Scholar 

  20. Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65, 55–63. https://doi.org/10.1016/0022-1759(83)90303-4.

    Article  Google Scholar 

  21. Drulis-Kawa, Z., & Dorotkiewicz-Jach, A. (2010). Liposomes as delivery systems for antibiotics. International Journal of Pharmaceutics, 387(1–2), 187–198. https://doi.org/10.1016/j.ijpharm.2009.11.033.

    Article  Google Scholar 

  22. Bushmakina, I. M., Martynova, M. A., & Knyazeva, E. V. (2015). XXI century: how our notions about liposomal drugs have been transformed. Pharmaceutical Chemistry Journal, 49(2), 111–119. https://doi.org/10.1007/s11094-015-1232-x.

    Article  Google Scholar 

  23. Park, J. P., Kim, J. H., Park, M. K., & Yun, J. W. (2011). Potential agents for cancer and obesity treatment with herbal medicines from the green garden. Biotechnology and Bioprocess Engineering, 16(6), 1065–1076. https://doi.org/10.1007/s12257-011-0215-3.

    Article  Google Scholar 

  24. Miao, Z. H., Tang, T., Zhang, Y. X., Zhang, J. S., & Ding, J. (2003). Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells. International Journal of Cancer, 106(1), 108–115. https://doi.org/10.1002/ijc.11174.

    Article  Google Scholar 

  25. Parrella, A., Lavorgna, M., Criscuolo, E., Russo, C., & Isidori, M. (2014). Estrogenic activity and cytotoxicity of six anticancer drugs detected in water systems. Science of the Total Environment, 485-486, 216–222. https://doi.org/10.1016/j.scitotenv.2014.03.050.

    Article  Google Scholar 

  26. Zhou, X., Zhang, Y., Li, Y., Hao, X., Liu, X., & Wang, Y. (2012). Azithromycin synergistically enhances anti-proliferative activity of vincristine in cervical and gastric cancer cells. Cancers (Basel), 4(4), 1318–1332. https://doi.org/10.3390/cancers4041318.

    Article  Google Scholar 

  27. Mishra, D., Singh, S., & Narayan, G. (2016). Curcumin induces apoptosis in pre-B acute lymphoblastic leukemia cell lines via PARP-1 cleavage. Asian Pacific Journal of Cancer Prevention, 17(8), 3865–3869.

    Google Scholar 

  28. Zhao, J. A., Sang, M. X., Geng, C. Z., Wang, S. J., & Shan, B. E. (2016). A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma. Oncology Letters, 12(5), 4252–4262. https://doi.org/10.3892/ol.2016.5126.

    Article  Google Scholar 

  29. Lutsenko, S. V., Feldman, N. B., Gumanov, S. G., Rodina, A. V., & Severin, S. E. (2000). Cytotoxic activity, accumulation, and intracellular distribution of anthracycline antibiotics and their conjugates with the epidermal growth factor in sensitive and resistant MCF-7 cells. Biochemistry (Mosc), 65(11), 1299–1304.

    Google Scholar 

  30. Lutsenko, S. V., Feldman, N. B., & Severin, S. E. (2002). Cytotoxic and antitumor activities of doxorubicin conjugates with the epidermal growth factor and its receptor-binding fragment. Journal of Drug Targeting, 10(7), 567–571. https://doi.org/10.1080/1061186021000038058.

    Article  Google Scholar 

  31. Lamprecht, A., & Benoit, J. P. (2006). Etoposide nanocarriers suppress glioma cell growth by intracellular drug delivery and simultaneous P-glycoprotein inhibition. Journal of Controlled Release, 112(2), 208–213. https://doi.org/10.1016/j.jconrel.2006.02.014.

    Article  Google Scholar 

  32. Ma, S., Li, M., Liu, N., Li, Y., Li, Z., Yang, Y., Yu, F., Hu, X., Liu, C., & Mei, X. (2017). Vincristine liposomes with smaller particle size have stronger diffusion ability in tumor and improve tumor accumulation of vincristine significantly. Oncotarget, 8(50), 87276–87291. https://doi.org/10.18632/oncotarget.20162.

    Article  Google Scholar 

  33. Kumar, A., Ahuja, A., Ali, J., & Baboota, S. (2016). Curcumin-loaded lipid nanocarrier for improving bioavailability, stability and cytotoxicity against malignant glioma cells. Drug Delivery, 23(1), 214–229. https://doi.org/10.3109/10717544.2014.909906.

    Article  Google Scholar 

  34. Javed, S., Kohli, K., & Ali, M. (2011). Reassessing bioavailability of silymarin. Alternative Medicine Review, 16(3), 239–249.

    Google Scholar 

  35. Lutsenko, S. V., Kiselev, S. M., & Severin, S. E. (2003). Molecular mechanisms of tumor angiogenesis. Biochemistry (Mosc), 68(3), 286–300. https://doi.org/10.1023/A:1023002216413.

    Article  Google Scholar 

  36. Drummond, D. C., Meyer, O., Hong, K., Kirpotin, D. B., & Papahadjopoulos, D. (1999). Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacological Reviews, 51(4), 691–743.

    Google Scholar 

  37. Sahoo, S. K., & Labhasetwar, V. (2003). Nanotech approaches to drug delivery and imaging. Drug Discovery Today, 8(24), 1112–1120. https://doi.org/10.1016/S1359-6446(03)02903-9.

    Article  Google Scholar 

Download references

Funding

The work has been supported by the Program of Competitive Growth of I.M. Sechenov First Moscow State Medical University.

Author information

Authors and Affiliations

  1. I.M. Sechenov First Moscow State Medical University, 8-2 Trubetskaya str., Moscow, Russian Federation, 119991

    Nataliya B. Feldman, Tatiana I. Gromovykh, Natalia E. Sedyakina, Ivan I. Krasnyuk Jr & Sergey V. Lutsenko

  2. All-Russian Research Institute of Medicinal and Aromatic Plants, Moscow, Russian Federation

    Nataliya B. Feldman

Authors
  1. Nataliya B. Feldman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tatiana I. Gromovykh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Natalia E. Sedyakina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ivan I. Krasnyuk Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sergey V. Lutsenko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nataliya B. Feldman.

Ethics declarations

Maintenance of animals and all procedures were conducted in accordance with the requirements of the legislation of the Russian Federation, the provisions of “European Convention for the protection of vertebrate animals used for experimental and other scientific purposes” (ETC 123), the provisions of the Guide for the Care and Use of Laboratory Animals (Washington D.C., 2011), and other rules of international law regulating the content and use of laboratory (experimental) animals. All animal experiments were approved by the All-Russian Research Institute of Medicinal and Aromatic Plants Bioethics Committee.

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Feldman, N.B., Gromovykh, T.I., Sedyakina, N.E. et al. Cytotoxic and Antitumor Activity of Liposomal Silibinin. BioNanoSci. 8, 971–976 (2018). https://doi.org/10.1007/s12668-018-0556-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12668-018-0556-x

Keywords

Search

Navigation