Tumoricidal Activity of RNase A and DNase I

Cover Page

Cite item

Abstract

In our work the antitumor and antimetastatic activities of RNase A and DNase I were studied using two murine models of pulmonary (Lewis lung carcinoma) and liver (hepatoma A-1) metastases. We found that intramuscular administration of RNase A at the dose range of 0.1-50 μg/kg retarded the primary tumor growth by 20-40%, and this effect disappeared with the increase in RNase A dose over 0.5 mg/kg. DNase I showed no effect on the primary tumor growth. The intramuscular administration of RNase A (0.35-7 μg/kg) or DNase I (0.02-2.3 mg/kg) resulted in a considerable decrease in the metastasis number into the lungs of animals with Lewis lung carcinoma and a decrease of the hepatic index of animals with hepatoma 1A. A histological analysis of the organs occupied by metastases revealed that the administration of RNase A and DNase I induced metastasis pathomorphism as manifested by the destruction of oncocytes, an increase in necrosis and apoptosis foci in metastases, and mononuclear infiltration. Our data indicated that RNase A and DNase I are highly promising as supplementary therapeutics for the treatment of metastasizing tumors.

Full Text

Tumoricidal Activity of RNase A and DNase I
×

About the authors

O A Patutina

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: marzen@niboch.nsc.ru

N L Mironova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: marzen@niboch.nsc.ru

E I Ryabchikova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: marzen@niboch.nsc.ru

N A Popova

Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences

Email: marzen@niboch.nsc.ru

V P Nikolin

Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences

Email: marzen@niboch.nsc.ru

V I Kaledin

Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences

Email: marzen@niboch.nsc.ru

V V Vlassov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: marzen@niboch.nsc.ru

M A Zenkova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: marzen@niboch.nsc.ru

References

  1. Dalmay T., Edwards D.R. // Oncogene. 2006. V. 25. no. 46. P. 6170-6175.
  2. Ardelt B., Ardelt W., Darzynkiewicz Z. // Cell Cycle. 2003. V. 2. no. 1. P. 22-24.
  3. Iorio M.V., Ferracin M., Liu C.G. et al. // Cancer Res. 2005. V. 65. no. 16. P. 7065-7070.
  4. Garcia-Olmo D., Garcia-Olmo D.C., Ontanon J. et al. // Blood. 2000. V. 95. no. 2. P. 724-735.
  5. Kotchetkov R., Cinatl J., Krivtchik A.A. et al. // Anticancer Res. 2001. V. 21. P. 1035-1042.
  6. Soucek J., Pouckova P., Matousek J. et al. // Neoplasma. 1996. V.43. no. 5. P. 335-340.
  7. Cinatl J.Jr., Cinatl J., Kotchetkov R. et al. // Int. J. Oncol. 1999. V. 15. no. 5. P. 1001-1009.
  8. Pouckova P., Zadinova M., Hlouskova D. et al. // J. Control Release. 2004. V. 95. no. 1. P. 83-92.
  9. Rybak S.M., Pearson J.W., Fogler W.E. et al. // J. Natl. Cancer Inst. 1996. V. 88. no. 11. P. 747-753.
  10. Lee I., Lee Y.H., Mikulski S.M. // J. Surg. Oncol 2000. V. 73. no. 3. P. 164-171.
  11. Costanzi J., Sidranski D., Navon A. et al. // Cancer Invest. 2005. V. 23. no. 7. P. 643-650.
  12. Ledoux L. // Nature. 1955. V. 175. no. 4449. P. 258-259.
  13. Ledoux L. // Nature. 1955. V. 176. no. 4470. P. 36-37.
  14. De Lamirande G. // Nature. 1961. V. 192. P. 52-54.
  15. Roth J.S. // Cancer Res. 1963. V. 23. P. 657-666.
  16. Klink T.A., Raines R.T. // J. Biol. Chem. 2000. V. 275. P. 17463-17467.
  17. Leland P.A., Schultz L.W., Kim B.M., Raines R.T. // Pro. Natl. Acad. Sci. USA. 1998. V. P. 10407-10412.
  18. Rutkoski T.J., Raines R.T. // Curr. Pharm. Biotechnol. 2008. V. 9. no. 3. P. 185-189.
  19. Wu Y., Mikulski S.M., Ardelt W. et al. // J. Biol Chem. 1993. V. 268. no. 14. P. 10686-10693.
  20. Kim J.S., Soucek J., Matousek J., Raines R.T. // J. Biol. Chem. 1995. V. 270. no. 18. P. 10525-10530.
  21. Sugihara S., Yamamoto T., Tanaka H. et al. // Br. J. Cancer. 1993. V. 67. P. 66-70.
  22. Tokita K., Sugihara S., Hiraoka T. et al. // Invasion Metastasis. 1995. V. 15. P. 46-59.
  23. Silberklang M., Gillum A.M., RhajBhandary // Methods Enzymol. 1979. V. 59. P. 58-109.
  24. Tomayko M.M., Reynolds C.P. // Cancer Chemother. Pharmacol. 1989. V. 24. P. 148-154.
  25. Klink T.A., Raines R.T. // Biol. Chem. 2000. V. 275. P. 17463-17467.
  26. Kim J.S., Soucek J., Matousek J. et al. // J. Biol. Chem. 1995. V. 270. P. 31097-31102.
  27. Matousek J. // Comp. Biochem. Physiol. C. 2001. V. 129. P. 175-191.
  28. Haigis M.C., Raines R.T. // J. Cell Sci. 2003. V. 116. P. 313-324.
  29. Zhao H., Ardelt B., Ardelt W. et al. // Cell Cycle. 2008. V. 7. P. 3258-3261.
  30. Sorrentino S., Naddeo M., Russo A. et al. // Biochemistry. 2003. V. 42. P. 10182-10190.
  31. Blaszczyk J., Gan J., Tropea J.E. et al. // Structure. 2004. V. 12. P. 457-466.
  32. Kojima K. // Nagoya J. Med. Sci. 1993. V. 56. P. 1-18.
  33. Ran S., Downes A., Thorpe P.E. // Cancer Res. 2002. V. 62. P. 6132-6140.
  34. Ilinskaya O.N., Dreyer F., Mitkevich V.A. et al. // Protein Sci. 2002. V. 11. P. 2522-2525.
  35. Ilinskaya O.N., Koschinski A., Mitkevich V.A. et al. // Biochem. Biophys. Res. Commun. 2004. V. 314. P. 550-554.
  36. Zhang B., Pan X., Cobb G.P. et al. // Dev. Biol. 2007. V. 302. P. 1-12.
  37. Wong T.S., Liu X.B., Wong B.Y. et al. // Clin. Cancer Res. 2008. V. 14. P. 2588-2592.
  38. Garzon R., Fabbri M., Cimmino A. et al. // Trends Mol. Med. 2006. V. 12. no. 12. P. 580587.
  39. Zhang B., Pan X., Cobb G. P. et al. // Dev. Biol. 2007. V. 302. no. 1. P. 1-12.
  40. Iorio M.V., Ferracin M., Liu C.G. et al. // Cancer Res. 2005. V. 65. no. 16. P. 7065-7070.
  41. Wong T.S., Liu X.B., Wong B.Y. et al. // Clin. Cancer Res. 2008. V. 14. no. 9. P. 2588-2592.
  42. Fauve R.M. // In: Azuma I., JollÈs G. (ed) Immunostimulants: Now and Tomorrow. 1987. Springer-Verlag, Berlin, pp.225-234.
  43. Januaz M., Wieczorek Z., Spiegel K. et al. // Mol. Immunol. 1987. V. 249. no. 10. P. 1029-1031.
  44. Vanhoof G., Goosens F., De Meester I. et al. // The FASEB Journal. 1995. V. 9. P. 736-744.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2010 Patutina O.A., Mironova N.L., Ryabchikova E.I., Popova N.A., Nikolin V.P., Kaledin V.I., Vlassov V.V., Zenkova M.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies