A mechanism of the toxicity of artificial ribonucleases for human cancer cells

  • E. B. Logashenko
  • I. L. Kuznetsova
  • E. I. Ryabchikova
  • V. V. Vlassov
  • M. A. Zenkova
Experimental Studies
  • 41 Downloads

Abstract

The ability of artificial ribonucleases, low molecular weight compounds exhibiting RNA cleavage in vitro, to cause human cancer cell death in a concentration-dependent manner has been studied. The cytotoxic effect of artificial ribonucleases on cells appeared at rather low concentrations of these compounds (10−5 M). The study of mechanisms of the cytotoxic effect has shown that in addition to ribonuclease activity these compounds exhibit membranotropic activity. This activity allows the compounds to penetrate effectively inside cells. The cytotoxic effect of artificial ribonucleases involves damage of cell membrane, detachment of plasmalemma and impairments of its macromolecular organization. However, in the case of shortterm exposure to these compounds, cells survive even with damaged membrane.

Key words

artificial ribonucleases citotoxicity membranotropic activity antineoplastic drugs 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Futami, J., Maeda, T., Kitazoe, M., Nukui, E., Tada, H., Seno, M., Kosaka, M., and Yamada, H., Biochemistry, 2001, vol. 40, pp. 7518–7524.CrossRefGoogle Scholar
  2. 2.
    Ardelt, W., Mikulski, S.M., and Shogen, K., J. Biol. Chem., 1991, vol. 266, pp. 245–251.Google Scholar
  3. 3.
    Iordanov, M.S., Ryabinina, O.P., Wong, J., Dinh, T.H., Newton, D.L., Rybak, S.M., and Magun, B.E., Cancer Res., 2000, vol. 60, pp. 1983–1994.Google Scholar
  4. 4.
    Grabarek, J., Ardelt, B., Du, L., and Darzynkiewicz, Z., Exp. Cell. Res., 2002, vol. 278, pp. 61–71.CrossRefGoogle Scholar
  5. 5.
    Niittymaki, T. and Lonnberg, H., Org. Biomol. Chem., 2006, vol. 4, pp. 15–25.CrossRefGoogle Scholar
  6. 6.
    Konevetz, D.A., Beck, I.E., Beloglazova, N.G., Sulimenkov, I.V., Sil’nikov, V.N., Zenkova, M.A., Shishkin, G.V., and Vlassov, V.V., Tetrahedron, 1999, vol. 55, pp. 503–512.CrossRefGoogle Scholar
  7. 7.
    Zenkova, M., Beloglazova, N., Sil’nikov, V., Vlassov, V., and Giege, R., Methods Enzymol., 2001, vol. 341, pp. 468–490.CrossRefGoogle Scholar
  8. 8.
    Koval’ov, N., Kuznetsova, I., Burakova, E., Sil’nikov, V., Zenkova, M., and Vlassov, V., Nucleosides Nucleotides Nucleic Acids, 2004, vol. 23, pp. 977–981.CrossRefGoogle Scholar
  9. 9.
    Chattopadhyay, N., Kher, R., and Godbole, M., Biotechniques, 1993, vol. 15, pp. 24–26.Google Scholar
  10. 10.
    Kostenko, E.V., Laktionov, P.P., Vlassov, V.V., and Zenkova, M.A., Biochim. Biophys. Acta, 2002, vol. 1576, pp. 143–147.Google Scholar
  11. 11.
    Park, J.G., Kramer, B.S., Steinberg, S.M., Carmichael, J., Collins, J.M., Minna, J.D., and Gazdar, A.F., Cancer Res., 1987, vol. 47, pp. 5875–5879.Google Scholar
  12. 12.
    Wilkie, B., Elektronnaya mikroscopiya dlya nachinayuschikh (Electron Microscopy For Beginners), Moscow: Mir, 1975.Google Scholar
  13. 13.
    Podyminogin, M.A., Vlassov, V.V., and Giege, R., Nucleic Acids Res., 1993, vol. 21, pp. 5950–5956.CrossRefGoogle Scholar
  14. 14.
    Mironova, N.L., Pyshnyi, D.V., Ivanova, E.M., Zenkova, M.A., Gross, H.J., and Vlassov, V.V., Nucleic Acids Res., 2004, vol. 32, pp. 1928–1936.CrossRefGoogle Scholar
  15. 15.
    Kovalev, N.A., Medvedeva, D.A., Zenkova, M.A., and Vlassov, V.V., Bioorg. Chem., 2008, vol. 36, pp. 33–45.Google Scholar
  16. 16.
    Carmichael, J., DeGraff, W.G., Gazdar, A.F., Minna, J.D., and Mitchell, J.B., Cancer Res., 1987, vol. 47, pp. 936–942.Google Scholar
  17. 17.
    Davies, A.A., Wigglesworth, N.M., Allan, D., Owens, R.J., and Crumpton, M.J., Biochem. J., 1984, vol. 219, pp. 301–308.Google Scholar
  18. 18.
    Ghobrial, I.M., Witzig, T.E., and Adjei, A.A., CA Cancer J. Clin., 2005, vol. 55, pp. 178–194.CrossRefGoogle Scholar
  19. 19.
    Saxena, S., Shogen, K., and Ardelt, W., Laboratory Medicine, 2003, vol. 34, pp. 380–387.CrossRefGoogle Scholar
  20. 20.
    Spalletti-Cernia, D., Sorrentino, R., Di Gaetano, S., Piccoli, R., Santoro, M., D’Alessio, G., Laccetti, P., and Vecchio, G., Br. J. Cancer, 2004, vol. 90, pp. 270–277.CrossRefGoogle Scholar
  21. 21.
    Lee, I., Kalota, A., Gewirtz, A.M., and Shogen, K., Anticancer Res., 2007, vol. 27(1A), pp. 299–307.Google Scholar
  22. 22.
    Reggiori, F. and Klionsky, D.J., Curr. Opin. Cell Biol., 2005, vol. 17, pp. 415–422.CrossRefGoogle Scholar
  23. 23.
    Makarov, A.A. and Ilinskaya, O.N., FEBS Lett., 2003, vol. 540, pp. 15–20.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2010

Authors and Affiliations

  • E. B. Logashenko
    • 1
  • I. L. Kuznetsova
    • 1
  • E. I. Ryabchikova
    • 1
  • V. V. Vlassov
    • 1
  • M. A. Zenkova
    • 1
  1. 1.Institute of Chemical Biology and Fundamental MedicineNovosibirskRussia

Personalised recommendations