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The influence of recombinant interferon α2β synthesized in plants on the reparative enzyme mgmt expression in human somatic cells in vitro

Nidoieva Z.M., Peterson A.A., Ruban T.P., Dzuba G.V., Kuchuk M.V., Lukash L.L.


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SUMMARY. The influence of recombinant interferon α2β synthe-sized in trasgenic plants on the expression of human repair protein O6-methylguanine-DNA methyltransfe-rase (MGMT) in both tumour and non-tumour ori-ginated cells was investigated. Human tumour Hp-2 cells (epidermoid carcinoma of the larynx) and non-tumour human E8 cells (originated in our laboratory from embrionic germ cells) were treated with purified recombinant interferon α2β in serum-free medium. Protein levels were determined by Western-blot method. Recombinant interferon α2β caused decrease in MGMT protein amount in tumour Hp-2 cells at all treated concentrations (2, 20, 200, 2000 IU/ml) relatively to the control level. In human non-tumour cells E8 we revealed a decrease in MGMT amount at two of the highest concentrations: 200 and 2000 IU/ml, although a statistically significant effect compared to the control level was observed only at a concentration of 200 IU/ml.

Tsitologiya i Genetika 2019, vol. 53, no. 6, pp. 36-43

E-mail: zarinanidoeva, lukash, nkuchuk

Nidoieva Z.M., Peterson A.A., Ruban T.P., Dzuba G.V., Kuchuk M.V., Lukash L.L. The influence of recombinant interferon α2β synthesized in plants on the reparative enzyme mgmt expression in human somatic cells in vitro, Tsitol Genet., 2019, vol. 53, no. 6, pp. 36-43.

In "Cytology and Genetics":
Z. M. Nidoieva, A. A. Peterson, T. P. Ruban, G. V. Dzuba, M. V. Kuchuk, L. L. Lukash The Influence of Recombinant Interferon α2b Synthesized in Plants on the Reparative Enzyme MGMT Expression in Human Somatic Cells in vitro, Cytol Genet., 2019, vol. 53, no. 6, pp. 467472
DOI: 10.3103/S0095452719060070


1. Verbeek, B., Southgate, T.D., Gilham, D.E., and Margison, G.P., O6-Methylguanine-DNA methyltransferase inactivation and chemotherapy, Br. Med. Bull., 2008, no. 85, pp. 1733.

2. Salam, T., Premila, DeviS., and Duncan, LyngdohR.H., Molecular criteria for mutagenesis by DNA methylation: Some computational elucidations, Mutat. Res, 2018, no. 807, pp. 1020.

3. Paredes, J.A., Ezerskyte, M., Bottai, M., and Dreij, K., Transcriptional mutagenesis reduces splicing fidelity in mammalian cells, Nucleic Acids Res., 2017, vol. 45, no. 11, pp. 65206529.

4. Uhlén, M., Fagerberg, L., Hallström, B.M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, E., Kampf, C., Sjöstedt, E., Asplund, A., Olsson, I., Edlund, K., Lundberg, E., Navani, S., Szigyarto, C.A., Odeberg, J., Djureinovic, D., Takanen, J.O., Hober, S., Alm, T., Edqvist, P.H., Berling, H., Tegel, H., Mulder, J., Rockberg, J., Nilsson, P., Schwenk, J.M., Hamsten, M., von Feilitzen, K., Forsberg, M., Persson, L., Johansson, F., Zwahlen, M., von Heijne, G., Nielsen, J., and Ponten, F., Proteomics. Tissue-based map of the human proteome, Science, 2015, vol. 347, no. 6220, p.1260419.

5. Stupp, R., Mason, W.P., Bent, M.J., Weller, M., Fisher, B., Taphoorn, M.J., Belanger, K., Brandes, A.A., Marosi, C., Bogdahn, U., Curschmann, J., Janzer, R.C., Ludwin, S.K., Gorlia, T., Allgeier, A., Lacombe, D., Cairncross, J.G., Eisenhauer, E., and Mirimanoff, R.O., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma, N. Engl. J. Med., 2005, no. 352, pp. 987996.

6. Gerson, S.L., Clinical relevance of MGMT in the treatment of cancer, J. Clin. Oncol., 2002, vol. 20, pp. 23882399.

7. Esteller, M. and Herman, J.G., Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer, Oncogene, 2004, vol. 23, no. 1, pp. 18.

8. Pegg, A.E., Multifaceted roles of alkyltransferase and related proteins in DNA repair, DNA damage, resistance to chemotherapy, and research tools, Chem. Res. Toxicol., 2011, vol. 24, pp. 618639.

9. Shen, D., Guo, C.C., Wang, J., Qiu, Z.K., Sai, K., Yang, Q.Y., Chen, Y.S., Chen, F.R., Wang, J., Panasci, L., and Chen, Z.P., Interferon-α/β enhances temozolomide activity against MGMT-positive glioma stem-like cells, Oncol. Rep., 2015, vol. 34, pp. 27152721.

10. Wang, B.X., Rahbar, R., and Fish, E.N., Interferon: current status and future prospects in cancer therapy, J. Interfer. Cytok. Res., 2011, vol. 31, no. 7, pp. 545552.

11. Parker, B.S., Rautela, J., and Hertzog, P.J., Antitumour actions of interferons: implications for cancer therapy, Nat. Rev. Cancer, 2016, vol. 16, no. 3, pp. 131144.

12. Dunn, G.P., Koebel, C.M., and Schreiber, R.D., Interferons, immunity and cancer immunoediting, Nat. Rev. Immunol, 2006, vol. 6, no. 11, pp. 836848.

13. Piconese, S., Pacella, I., Timperi, E., and Barnaba, V., Divergent effects of type-I interferons on regulatory T cells, Cytokine Growth Factor Rev., 2015, vol. 26, no. 2, pp. 13341.

14. Medrano, R.F.V., Hunger, A., Mendonca, S.A., Barbuto, J.A.M., and Strauss, B.E., Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy, Oncotarget, 2017, vol. 8, no. 41, pp. 7124971284.

15. Ma, H., Jin, S., Yang, W., Tian, Z., Liu, S., Wang, Y., Zhou, G., Zhao, M., Gvetadze, S., Zhang, Z., and Hu, J., Interferon-α promotes the expression of cancer stem cell markers in oral squamous cell carcinoma, J. Cancer, 2017, vol. 8, no. 12, pp. 23842393.

16. Vasquez, M., Fioravanti, J., Aranda, F., Paredes, V., Gomar, C., Ardaiz, N., Fernandez-Ruiz, V., Méndez, M., Nistal-Villan, E., Larrea, E., Gao, Q., Gonzalez-Aseguinolaza, G., Prieto, J., and Berraondo, P., Interferon alpha bioactivity critically depends on Scavenger receptor class B type I function, Oncoimmunology, 2016, vol. 5, no. 8, pp. e1196309.

17. Yu, Y., Huang, R., Zong, X., He, X., and Mo, W., INFα-2b inhibitory effects on CD4(+)CD25(+) FOXP3(+) regulatory T cells in the tumor microenvironment of C57BL/6 J mice with melanoma xenografts, BMC Cancer, 2016, vol. 16, pp. 397.

18. Kotsarenko, K., Lylo, V., Ruban, T., Macewicz, L., and Lukash, L., Effects of some growth factors and cytokines on the expression of the repair enzyme MGMT and protein MARP in human cells in vitro: effect of some growth factors and cytokines, Biochem. Genet., 2018, vol. 56, no. 5, pp. 459477.

19. Sindarovska, Y.R., Gerasimenko, Y.V., Olevinskaya, Z.M., Spivak, N.Y., and Kuchuk, N.V., Production of human interferon alpha 2b in plants of Nicotiana excelsior by Agrobacterium-mediated transient expression, Cytol. Genet., 2010, vol. 44, no. 5, pp. 313316.

20. Budzianowski, J., Tobaccoa producer of recombinant interferons, Przegl. Lek., 2014, vol. 71, no. 11, pp. 639643.

21. Green, S.J. and Michael, R., Molecular Cloning, New York: Cold Spring Harbor Laboratory Press, 2012.

22. Nidoieva, Z.M., Samoilenko, I.O., Pidpala, O.V., Lukash, L.L., and Iatsyshyna, A.P., Bioinformatic search of hormone response elements within the human O6-methylguanine-DNA methyltransferase (MGMT) gene promoter, Factors Exp. Evol. Organ., 2015, vol. 17, pp. 7478.

23. Lavon, I., Fuchs, D., Zrihan, D., Efroni, G., Zelikovitch, B., Fellig, Y., and Siegal, T., Novel mechanism whereby nuclear factor kappaB mediates DNA damage repair through regulation of O(6)-methylguanine-DNA-methyltransferase, Cancer Res., 2007, vol. 67, no. 18, pp. 89528959.

24. Costello, J.F., Futscher, B.W., Kroes, R.A., and Pieper, R.O., Methylation-related chromatin structure is associated with exclusion of transcription factors from and suppressed expression of the O-6-methylguanine DNA methyltransferase gene in human glioma cell, Mol. Cell Biol., 1994, vol. 14, no. 10, pp. 65156521.

25. Bhakat, K.K. and Mitra, S., Regulation of the human O(6)-methylguanine-DNA methyltransferase gene by transcriptional coactivators cAMP response element-binding protein-binding protein and p300, J. Biol. Chem., 2000, vol. 3, no. 275, pp. 3419734204.

26. de Veer, M.J., Holko, M., Frevel, M., Walker, E., Der, S., Paranjape, J.M., Silverman, R.H., and Williams, B.R., Functional classification of interferon-stimulated genes identified using microarrays, J. Leukoc. Biol., 2001, vol. 69, no. 6, pp. 912920.

27. Weaver, K.D., Yeyeodu, S., Cusack, J.C., Jr., Baldwin, A.S., Jr., and Ewend, M.G., Potentiation of chemotherapeutic agents following antagonism of nuclear factor κB in human gliomas, J. Neurooncol. 2003, vol. 61, pp. 187196.

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