Drug with Neuroprotective Properties Noopept Does Not Stimulate Cell Proliferation

Effects of Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) on the relative level of proliferation marker Ki-67 and cell cycle parameters were studied in HEK293 and SH-SY5Y cell lines. The previously established multifactorial mechanism of action of the drug includes enhancement of neurotrophin NGF and BDNF expression and increase in HIF-1 activity. The possible mitogenic action of Noopept was estimated by its effect on cell proliferation. Noopept did not affect cell distribution over G1, S, G2 cell cycle phases and the relative level of proliferation marker Ki-67 in the cell lines under study. These data suggest that Noopept does not stimulate cell growth.

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

References

  1. 1.

    Andreeva NA, Stel’mashuk EV, Isaev NK, Ostrovskaya RU, Gudasheva TA, Viktorov IV. Neuroprotective properties of nootropic dipeptide GVS-111 in in vitro oxygen-glucose deprivation, glutamate toxicity and oxidative stress. Bull. Exp. Biol. Med. 2000;130(10):969-972.

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    Antipova TA, Nikolaev SV, Ostrovskaya PU, Gudasheva TA, Seredenin SB. Dipeptide Piracetam Analogue Noopept Improves Viability of Hippocampal HT-22 Neurons in the Glutamate Toxicity Model. Bull. Exp. Biol. Med. 2016;161(1):58-60.

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Vakhitova YV, Sadovnikov SV, Borisevich SS, Ostrovskaya RU, Gudasheva TA, Seredenin SB. Molecular mechanism underlying the action of substituted Pro-Gly dipeptide Noopept. Acta Naturae. 2016;8(1):82-89.

    CAS  Article  Google Scholar 

  4. 4.

    Ostrovskaya RU, Vakhitova YuV, Salimgareeva MKh, Yamidanov RS, Sadovnikov SV, Kapitsa IG, Seredenin SB. On the mechanism of Noopept action: decrease in activity of stressinduced kinases and increase in expression of neutrophines. Eksp. Klin. Farmakol. 2010;73(12):2-5. Russian.

    Google Scholar 

  5. 5.

    Ostrovskaya RU, Gudasheva TA, Voronina TA, Seredenin SB. The novel nootropic and neuroprotector drug Noopept (GVS-111). Eksp. Klin. Farmakol. 2002;65(5):66-72. Russian.

    CAS  Google Scholar 

  6. 6.

    Ostrovskaya RU, Gudasheva TA, Zaplina AP, Vahitova JV, Salimgareeva MH, Jamidanov RS, Seredenin SB. Noopept stimulates the expression of NGF and BDNF in rat hippocampus. Bull. Exp. Biol. Med. 2008;146(3):334-337.

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Descamps S, Toillon RA, Adriaenssens E, Pawlowski V, Cool SM, Nurcombe V, Le Bourhis X, Boilly B, Peyrat JP, Hondermarck H. Nerve growth factor stimulates proliferation and survival of human breast cancer cells through two distinct signaling pathways. J. Biol. Chem. 2001;276(21):17 864-17 870.

  8. 8.

    Jia X, Gharibyan AL, Öhman A, Liu Y, Olofsson A, Morozova-Roche LA. Neuroprotective and nootropic drug Noopept rescues α-synuclein amyloid cytotoxicity. J. Mol. Biol. 2011;414(5):699-712.

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Ostrovskaya RU, Vakhitova YV, Kuzmina USh, Salimgareeva MKh, Zainullina LF, Gudasheva TA, Vakhitov VA, Seredenin SB. Neuroprotective effect of novel cognitive enhancer Noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation. J. Biomed. Sci. 2014;21:74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Paul SA, Simons JW, Mabjeesh NJ. HIF at the crossroads between ischemia and carcinogenesis. J. Cell. Physiol. 2004;200(1):20-30.

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Pelsman A, Hoyo-Vadillo C, Gudasheva TA, Seredenin SB, Ostrovskaya RU, Busciglio J. GVS-111 prevents oxidative damage and apoptosis in normal and Down’s syndrome human cortical neurons. Int. J. Dev. Neurosci. 2003;21(3):117-124.

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J. Cell. Physiol. 2000;182(3):311-322.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Seredenin SB, Voronina TA, Gudasheva TA, Ostrovskaya RU, Rozantsev GG, Skoldinov AP, Trofimov SS, Halikas J, Garibova TL. Biologically active N-acylprolyldipeptides having antiamnestic, antihypoxic effects. Patent No. 5.439.930 USA (1995).

  14. 14.

    Tovar-y-Romo LB, Penagos-Puig A, Ramírez-Jarquín JO. Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate. J. Neurochem. 2016;136(1):13-27.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Yu. V. Vakhitova.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 166, No. 10, pp. 457-460, October, 2018

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zainullina, L.F., Ivanova, T.V., Ostrovskaya, R.U. et al. Drug with Neuroprotective Properties Noopept Does Not Stimulate Cell Proliferation. Bull Exp Biol Med 166, 466–468 (2019). https://doi.org/10.1007/s10517-019-04373-8

Download citation

Key Words

  • Pro-Gly substituted dipeptides
  • Noopept
  • proliferation
  • cell cycle
  • Ki-67