Russian Journal of Genetics

, Volume 51, Issue 2, pp 130–137 | Cite as

Comparative analysis of natural and synthetic antimutagens as regulators of gene expression in human cells under exposure to ionizing radiation

  • V. F. Mikhailov
  • A. A. Shishkina
  • I. M. Vasilyeva
  • L. V. Shulenina
  • N. F. Raeva
  • E. A. Rogozhin
  • M. I. Startsev
  • G. D. Zasukhina
  • S. P. Gromov
  • M. V. Alfimov
General Genetics


This paper studies the effect of plant peptides of thionine Ns-W2 extracted from seeds of fennel flower (Nigella sativa) and β-purothionine from wheat germs (Triticum kiharae), as well as a synthetic antimutagen (crown-compound), on the expression of several genes involved in the control of cellular homeostasis, processes of carcinogenesis, and radiation response in human rhabdomyosarcoma cells (RD cells), T-lymphoblastoid cell line Jurkat, and blood cells. All of these agents acted as antimutagens-anticarcinogens, reducing the expression of genes involved in carcinogenesis (genes of families MMP, TIMP, and IAP and G-protein genes) in a tumor cell. A pronounced reduction in the mRNA level of these genes was caused by thionine Ns-W2, and the least effect was demonstrated by β-purothionine. Antimutagens had very little effect on the mRNA levels of the several studied genes in normal blood cells. Thionine Ns-W2 in tumor cells resulted in a reduction of the content of oncogenic mature miR-21 but did not affect the mRNA level of gene p53 and mature miR-34, which was regulated by the activity of tumor suppressor p53. It was established that thionine Ns-W2 has a cytotoxic effect by inducing the death of RD cells and lymphoma. The exposure of these cells to ionizing radiation enhanced the inhibitory effect of thionine on expression of the genes involved in oncogenesis. These data indicate that thionine can be regarded as a promising anticarcinogen.


Radiation Response Nigella Sativa Jurkat Cell Line Anti Cancer Normal Blood Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Paul, S. and Amundson, S., Gene expression signature of radiation exposure in peripheral white blood cells of smokers and non-smokers, Int. J. Radiat. Biol., 2011, vol. 87, no. 8, pp. 791–801.CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Takahashi, A., Suzuki, H., Omori, K., et al., The expression of p53-regulated genes in human cultured lymphoblastoid TSSE5 and WTK1 cell lines during spaceflight, Int. J. Rad. Res., 2010, vol. 86, no. 8, pp. 669–681.CrossRefGoogle Scholar
  3. 3.
    Morandi, E., Severini, C., Quercioli, D., et al., Gene expression changes in medical workers exposed to radiation, Radiat. Res., 2009, vol. 172, pp. 500–508.CrossRefPubMedGoogle Scholar
  4. 4.
    Chaudry, M. and Omaruddin, R., Differential regulation of micro RNA expression in irradiated and bystander cells, Mol. Biol., 2012, vol. 46, no. 4, pp. 634–643.Google Scholar
  5. 5.
    Erson-Bensan, A., Introduction to micro RNAs in biological systems, in Methods in Molecular Biology, Springer-Verlag, 2014, vol. 1107, pp. 1–14.CrossRefPubMedGoogle Scholar
  6. 6.
    Templin, T., Amundson, S., Brenner, D., et al., Whole mouse blood micro RNA as biomarkers for exposure to γ-rays and Fe56 ions, Int. J. Rad. Res., 2011, vol. 87, no. 7, pp. 653–662.CrossRefGoogle Scholar
  7. 7.
    Coppola, V., Mucumeci, M., Patrizii, M., et al., BTG2 loss and miR-21 upregulation contribute to prostate cell transformation by inducing luminal markers expression and epithelial-mesenchymal transition, Oncogene, 2013, vol. 32, pp. 1843–1853.CrossRefPubMedGoogle Scholar
  8. 8.
    Avci, C. and Baran, G., Use of micro RNAs in personalized medicine, in Methods in Molecular Biology, Springer-Verlag, 2014, vol. 1107, pp. 311–325.CrossRefPubMedGoogle Scholar
  9. 9.
    Yin, D., Ogawa, S., Kawamata, N., et al., MiR-34 functions as a tumor suppressor modulating EGFR in glioblastoma multiforme, Oncogene, 2013, vol. 32, pp. 1155–1163.CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Chaudhry, M., Kreger, B., and Omaruddin, R., Transcription modulation of micro-RNA in human cells differing in radiation sensitivity, Int. J. Radiat. Biol., 2010, vol. 86, no. 7, pp. 569–583.CrossRefPubMedGoogle Scholar
  11. 11.
    Zasukhina, G.D., Shishkina, A.A., Vasil’eva, I.M., et al., Comparative analysis of gene expression in human blood cells and in rhabdomyosarcoma cells pretreated with antimutagens, Dokl. Biol. Sci., 2014, vol. 457, no. 1, pp. 160–162.Google Scholar
  12. 12.
    Zasukhina, G.D., Semyachkina, A.N., Vasil’eva, I.M., et al., Comparison of the antimutagenic activities of natural and synthetic substances in irradiated repairdefective human cells, Dokl. Biol. Sci., 2006, vol. 408, nos. 1–6, pp. 269–271.CrossRefPubMedGoogle Scholar
  13. 13.
    Zasukhina, G.D., Mechanisms of human cell resistance to mutagens, Biol. Bull. Rev., 2011, vol. 1, no. 6, pp. 496–508.CrossRefGoogle Scholar
  14. 14.
    Zasukhina, G.D., Odintsova, T.I., Shulenina, L.V., et al., Antimutagens (β-purothionin and crown compound) as modulators of expression of genes involved in carcinogenesis in human cell, Dokl. Biochem. Biophys., 2012, vol. 446, nos. 1–6, pp. 254–256.CrossRefPubMedGoogle Scholar
  15. 15.
    Arushanyan, E.B., Systemic and cellular mechanisms of anti-tumor activity of plant adaptogens, Vopr. Onkol., 2009, vol. 55, no. 1, pp. 15–23.Google Scholar
  16. 16.
    Owini, S., A study of the effect of some plant extracts on certain malignant cell lines in vitro, Gaza: Islamic Univ., 2006, pp. 1–38.Google Scholar
  17. 17.
    Elkady, A., Crude extract of Nigella sativa inhibits proliferation and induces apoptosis in human cervical carcinoma HeLa cells, Afric. J. Biotechnol., 2012, vol. 11, pp. 12710–12720.Google Scholar
  18. 18.
    Bocharova, O.A., Bocharov, U.V., Karpova, R.V., et al., Integrins LFA-1 and MAC-1 and cytokines IL-6 and IL-10 in high-cancer mice under the influence of phytoadaptogen, Bull. Exp. Biol. Med., 2014, vol. 157, no. 2, pp. 258–260.CrossRefPubMedGoogle Scholar
  19. 19.
    Durnev, A.D., Modification of a mutation process in human cells, Vestn. Ross. Akad. Med. Nauk, 2001, vol. 10, pp. 70–76.PubMedGoogle Scholar
  20. 20.
    Abilev, S.K., Glazer, V.M., and Aslanyan, M.M., Osnovy mutageneza i gipotoksikologii (Basics of Mutagenesis and Hypotoxicology), Moscow: Nestor-Istoriya, 2011.Google Scholar
  21. 21.
    Korman, D.B., Green tea, a promising source of novel antitumor drugs?, Vopr. Onkol., 2010, vol. 56, no. 3, pp. 262–271.PubMedGoogle Scholar
  22. 22.
    Anisimov, V.N., Zabezhinskii, M.A., Popovich, I.T., et al., Modern approaches to the study of carcinogenic security, antitumor, anticancer, and geroprotective activity of pharmacological agents, Vopr. Onkol., 2012, vol. 58, no. 1, pp. 7–18.PubMedGoogle Scholar
  23. 23.
    Tembhurne, S.V., Feroz, S., More, B.H., and Sakarkar, D.M., A review on therapeutic potential of Nigella sativa (kalonji) seeds, J. Med. Plants Res., 2014, vol. 8, no. 3, pp. 167–177.CrossRefGoogle Scholar
  24. 24.
    Badary, O.A., Nagi, M.N., Al-Shabanah, O.A., et al., Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity, Can. J. Physiol. Pharmacol., 1997, vol. 75, no. 12, pp. 1356–1361.CrossRefPubMedGoogle Scholar
  25. 25.
    Al-Shabanah, O.A., Badary, O.A., Nagi, M.N., et al., Thymoquinone protects against doxorubicin-induced cardiotoxicity without compromising its antitumor activity, J. Exp. Clin. Cancer Res., 1998, vol. 17, no. 2, pp. 193–198.PubMedGoogle Scholar
  26. 26.
    Gali-Muhtasib, H., Roessner, A., and SchneiderStock, R., Thymoquinone: a promising anti-cancer drug from natural sources, Int. J. Biochem. Cell Biol., 2006, vol. 38, no. 8, pp. 1249–1253.CrossRefPubMedGoogle Scholar
  27. 27.
    Effenberger-Neidnicht, K., Breyer, S., Mahal, K., et al., Cellular localization of antitumoral 6-alkyl thymoquinones revealed by an alkyne-azide click reaction and the streptavidin-biotin system, ChemBioChem, 2011, vol. 12, no. 8, pp. 1237–1241.CrossRefPubMedGoogle Scholar
  28. 28.
    Rogozhin, E.A., Oshchepkova, Y.I., Odintsova, T.I., et al., Novel antifungal defensins from Nigella sativa L. seeds, Plant Physiol. Biochem., 2011, vol. 49, no. 2, pp. 131–137.CrossRefPubMedGoogle Scholar
  29. 29.
    Egorov, Ts.A. and Odintsova, T.I., Defense peptides of plant immunity, Russ. J. Bioorg. Chem., 2012, vol. 38, no. 1, pp. 7–17.Google Scholar
  30. 30.
    Keller, U., Doucet, A., and Overall, C., Protease research in the era of system biology, Biol. Chem., 2007, vol. 388, no. 11, pp. 1159–1162.CrossRefGoogle Scholar
  31. 31.
    Zheltukhin, A.O. and Chumakov, P.M., Regular and inducible functions of the P53 gene, Usp. Biol. Khim., 2010, vol. 50, pp. 447–516.Google Scholar
  32. 32.
    He, L., He, X., Lim, L.P., et al., A microRNA component of the p53 tumor suppressor network, Nature, 2007, vol. 447, no. 7148, pp. 1130–1134.CrossRefPubMedGoogle Scholar
  33. 33.
    Pogosova-Agadjanyan, E., Fan, W., Georges, G., et al., Identification of radiation-induced expression changes in nonimmortalized human T-cells, Radiat. Res., 2011, vol. 175, no. 2, pp. 172–184.CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Kobacic, S., Mackay, A., Tamber, N., et al., Gene expression following ionizing radiation: identification of biomarkers for dose estimation and prediction of individual response, Int. J. Radiat. Biol., 2011, vol. 87, no. 2, pp. 115–129.CrossRefGoogle Scholar
  35. 35.
    Smirnov, D.A., Morley, M., Shin, E., et al., Genetic analysis of radiation-induced changes in human gene expression, Nature, 2009, vol. 459, no. 28, pp. 587–591.CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Kralj, M., Tusek-Bozik, L., and Erkanec, L., Biomedical potentials of crown ethers: prospective antitumor agents, ChemMedChem, 2008, vol. 3, pp. 1478–1492.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2015

Authors and Affiliations

  • V. F. Mikhailov
    • 1
  • A. A. Shishkina
    • 1
  • I. M. Vasilyeva
    • 2
  • L. V. Shulenina
    • 1
  • N. F. Raeva
    • 1
  • E. A. Rogozhin
    • 3
  • M. I. Startsev
    • 1
  • G. D. Zasukhina
    • 2
  • S. P. Gromov
    • 4
  • M. V. Alfimov
    • 4
  1. 1.Burnazyan Federal Medical Biophysical CenterFederal Medical-Biological AgencyMoscowRussia
  2. 2.Vavilov Institute of General GeneticsRussian Academy of SciencesMoscowRussia
  3. 3.Shemyakin-Ovchinnikov Institute of Bioorganic ChemistryRussian Academy of SciencesMoscowRussia
  4. 4.Centre of PhotochemistryRussian Academy of SciencesMoscowRussia

Personalised recommendations