Noncanonical DNA-binding properties of potential components of an antitumor composition (cytokine AIMP1/p43, lectin SNA, izatizon), which are able to affect different targets

  • O. Yu. Tsuvariev
  • O. V. Starozhuk
  • I. S. Karpova
  • L. G. Palchykovska
  • L. A. Zayika
  • T. V. Shyrina
  • V. V. Lylo
  • O. I. Kornelyuk
DOI: https://doi.org/10.7124/FEEO.v22.969

Abstract

Aim. To search the DNA-binding properties of various drugs promising for the creation of the antitumor composition (AIMP1/p43, SNA-I, izatizon), as well as their ability to influence on key matrix processes – DNA transcription and replication, which are a sensitive target for the action of many pharmacological drugs. Methods. The recombinant protein AIMP1/p43 was obtained from supernatant of E.coli lysed cells by metallic chelating chromatography on a Ni‑NTA‑agarose column. Also there were used the elderberry bark lectin SNA-I (LECTINOTEST, Ukraine), and the preparation of own production izatizon (IMBG NAS of Ukraine). The DNA-binding ability of the drugs was investigated by EMSA. As a transcription test system, an enzyme complex of DNA-dependent RNA polymerase of T7 bacteriophage and plasmid DNA pTZ19R * were used. PCR with Taq DNA polymerase and the plasmid pTZ19R * was used as the model replicative system. Results. Experimental conditions, in which the specificity of each drug action appeared, were found: the cytokine AIMP1/p43 and the SNA-I demonstrated the ability to bind to DNA by the EMSA test; izatizon induced structural changes in DNA, blocked the amplification of DNA during the PCR process, and also in vitro transcription with the participation of DNA-dependent RNA polymerase of the bacteriophage T7. Conclusions. Each of the selected drugs, which according to the literature data have antitumor potential, has demonstrated the ability to interact with the model supercoiled plasmid DNA pTZ19R *. The different ways of the selected drugs influence on DNA allows us to expect their effective combined action and synergism in case of their application as a common antitumor composition.

Keywords: cytokine AIMP1/p43, SNA-I, izatizon, EMSA method, transcription inhibiting, amplification blocking.

References

Dmitrenko V.V., Avdieiev S.S., Areshkov P.O., Balynska O.V., Bukreieva T.V., Stepanenko A.A., Chausovskii T.I. Kavsan V.M. From reverse transcription to human brain tumors. Biopolym. and Cell. 2013. Vol. 29. P. 221–233. doi: 10.7124/bc.00081C

Wolfe C.L., Warrington J.A., Davis S., Green S. Norcum M.T. Isolation and characterization of human nuclear and cytosolic multisynthetase complexes and the intracellular distribution of p43/EMAPII. Protein Sci. 2003. V. 12. P. 2282–2290. doi: 10.1110/ps.03147903

Quevillon S., Agou F., Robinson J-C., Mirande M. The p43 component of the mammalian multi-synthetase complex is likely to be the precursor of the endothelial monocyte-activating polypeptideII cytokine. J. Biol. Chem. 1997. Vol. 272. P. 32573–32579. doi: 10.1074/jbc.272.51.32573

Schwarz R.E., Schwarz M.A. In vivo therapy of local tumour progression by targeting vascular endhothelium with EMAP II. J. Surg. Res. 2004. Vol. 120. P. 64–72. doi: 10.1016/j.jss.2003.10.005

Liu B., Bian H., Bao J. Plant lectins: Potential antineoplastic drugs from bench to clinic. Cancer Letters. 2010. Vol. 287. P. 1–12. doi: 10.1016/j.canlet.2009.05.013

Lahtin V.M., Afanasev S.S., Aleshkin V.A., Nesvizhskiy Yu.V., Lahtin M.V., Shubin V.V., Cherepanova Yu.V., Pospelova V.V. Classification of lectins as universal regulatory molecules of biological systems. Bulletin of the Russian Academy of Medical Sciences. 2009. Vol. 3. P. 36–43.

Antoniuk V.O. Lectins and their raw sources. Lviv: Danila Galitsky LNMU Printing House, 2005. P. 554

Muñoz R., Arias Y., Ferreras J.M., Rojo M.A., Gayoso M.J., Nocito M., Benitez J., Jimenez P., Bernabeu C., Girbes T. Targeting a marker of the tumor neovasculature using a novel anti-human CD105-immunotoxin containing the non-toxic type 2 ribosome-inactivating protein nigrin b. Cancer Lett. 2007. Vol. 256. P. 73–80. doi: 10.1016/j.canlet.2007.05.012

Zayika L.A, Bolsunova O.I, Patskovskiy U.V., Rubashevskiy E.L., Dyadyun S.T., Rybalko S.L., Potopalsky A.I. Antiviral drug izatizon has no mutagenic effect and stimulates the proliferation of cells of the immune system. Biopolim. and Cell. 1995. Vol. 11(6). P. 89–95. doi: 10.7124/bc.000409

Zayika L.A, Bolsunova O.I, Potopalsky A.I. Antiviral, anticancer and immunomodulatory properties of therapeutic drug IZATIZON. Kyiv: Kolobih. 2010. 212 p.

Potopalsky A., Bolsunova O., Zaika L. New methods for molecular genetic recovery of humans and environment. Saarbrucken: LAP LAMBERT Academic Publishing. 2014. 123 p.

Zayika L., Bolsunova O., Potopalsky A., Didenko G., Kruts H. Analisis of antitumor and metastastik effects of izatizon and its analoge izatizon+Ag on Levis carcinoma of mice C57Bl6. International Internet Conference of the 2nd International scientific and practical forum: materials digest (collective monograph) (London, 3–7 October 2016). 2016. P. 78–80.

Vieira-Breitwieser O. Leguminous lectins bind non specifically to DNA: PhD thesis. Koln: Universitat. 2004. 270 p.

Palchykovska L.H., Vasylchenko O.V., Platonov M.O., Starosyla D.B., Porva Yu.I., Rymar S.Iu., Atamaniuk V.P., Samiilenko S.P., Rybalko S.L. Antiviral properties of plant flavonoids - inhibitors of DNA and RNA synthesis. Biopolymers and Cell. 2013. Vol. 29. P. 150–156. doi: 10.7124/bc.000813.

Bolsunova O., Brovarets O., Govorun D., Zaika L., Potopalsky A. Quantum Chemical Analysis of Structural and Conformational Properties of Methisazone and Prototropic Tautomerism of Izatin. International Review of Biophysical Chemistry. 2011. Vol. 2. P. 159–164. doi: 10.15866/irebic.v2i5.1537

Renault L., Kerjan P., Pasqualato S., Menetrey J., Robinson J.C., Kawaguchi S., Vassylyev D.G., Yokoyama S., Mirande M., Cherfils J. Structure of the EMAPII domain of human aminoacyl-tRNA synthetase complex reveals evolutionary dimer mimicry. EMBO J. 2001. Vol. 20. P. 570–578. doi: 10.1093/emboj/20.3.570

Frantz J.D., Gilbert W. A Novel Yeast Gene Product, G4p1, with a Specific Affinity for Quadruplex Nucleic Acids. The Journal of Biological Chemistry. 1995. Vol. 270. P. 20692–20697. doi: 10.1074/jbc.270.35.20692