Investigation of effect of EMAP II cytokine nanocomposite complex with dextran 70 on the BALB/C mice lines

L. Kolomiiets, V. Zayets, O. Tsuvariev, A. Kornelyuk
Institute of Molocular Biology and Genetics of NASU, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; 1 - Institute of Molocular Biology and Genetics of NASU, Kyiv; 2 - Taras Shevchenko National University of Kyiv, Kyiv


The cytokine ЕМАР ІІ is endothelial and monocytic-activating polypeptide II, the precursor of which is the component of the high-molecular complex aminoacyl-tRNA synthetase of the higher eukaryotes of the protein p43, is capable of modulating the properties of endothelial cells, monocytes and leukocytes. In low concentrations the cytokine stimulates and in high concentrations it suppresses the migration of endothelial cells, stimulates their apoptosis, affects the activity of monocytes, neutrophils, macrophages, thus contributing to inflammatory and necrotic processes in malignant tumors. One of the promising directions of targeted therapy of oncological diseases is the use of antiangiogenic, prokoagulative and proapoptic drugs, which became the basis for the selection of an antitumor cytokine ЕМАР ІІ as an object of research.  In the Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, the biotechnology of bacterial expression of recombinant ЕМАР ІІ in E.coli BL21 (DE3) cells and isolation of highly purified cytokine preparations in preparative amounts have been developed. In order to increase the stability and reduce the aggregation of recombinant ЕМАР ІІ, scientific and methodological foundations were created and nanocomposite complexes of the cytokine EMAR II with biocompatible polymers with cyclodextrin and dextran 70 were obtained. In this experimental work, the effects of the nanocomposite complex EMAR II and dextran-70 on the animal organism were investigated for the purpose of establishing safety of its use.  BALB / C mice were used as an object of research. Experimental studies have shown that acute and chronic administration of the drug to animals at doses of 300 – 10 000 μg / kg does not show the general toxic effects of the nanocomposite complex on the organism of mice. The obtained data open the prospect of further investigation of antitumor properties of the nanocomposite complex EMAR II with dextran-70  with the aim of possible further introduction into pharmacological practice.


nanocomposite complex ЕМАР ІІ, acute toxicity, chronic toxicity

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Glick B, Pasternak J. Molecular biotechnology. Principles and applications. Moscow: Mir. 2002; 589.

Adrio JL, Demain AL. Recombinant organisms for production of industrial products. Bioeng. Bugs. 2010;1(2):116-131.

Sahdev S, Khattar SK, Saini KS. Production of active eucariotic proteins through bacterial expression systems: a review of the existing biotechnology strategies. Mol Cell Biochem. 2008; 307 (2): 249-264.

Rosano GL, Cessarelli EA. Recombinant protein expression in Escherichia coli: advances and challenges. Frontiers in Microbiol. 2014;

( ): 1-17. 5. Kornelyuk AI, Babenko LA, Kozlov AV, Reznikov AG, Chaikovska LV, Polyakova LІ.Application for Invention "Nanocomposite anti-cancer agent". UA. Patent 17851 / ZU / 11, August 29, 2011.

Kao J, Ryan J, Brett G, et al. Endothelial monocyte activating polypeptide II. A novel tumor-derived polypeptide that activates host-response mechanisms. J Biol Chem. 1992; 267 ( ): 20239-20247.

Shalak V, Kaminska M, Mitnacht-Kraus R, Vandenabeele P, Clauss M, Mirande M. The EMAPII cytokine is released from the mammalian multisynthetase complex after cleavage of its p43/proEMAPII component. J Biol Chem. 2001; 276 ( ): 23769–76.

Berger AC, Tang G, Alexander HR, Libutti SK. Endothelial monocyte-activating polypeptide II, a tumor-derived monocyte-activating polypeptide II, that plays an important role in inflammation, apoptosis, and angiogenesis. J Immunother 2000; 23 ( ): 519–27.

Schwarz MA, Kandel J, Brett J et al. Endothelial-monocyte activating polypeptide II, a novel antitumour cytokine that suppresses primary and metastatic tumour growth and induces apoptosis in growing endothelial cells. J Exp Med.1999; 190 ( ): 341-54.

Chen J, Liu L, Liu X, Qui C, Meng F, Ma J, Lin Y, Xue Y. Lou-dose Endothelial monocyte activating polypeptide II induced autophagy by downregulation miR-20a in U-87 and U-251 glioma cells. Frontiers in Cellular Neuroscience. 2016; 10 ( ):

van Horssen R, Eggermont AM, ten Hagen TL. Endothelial monocyte-activating polypeptide II and its functions in (patho)physiological processes. Cytokine Growth Factor Rev. 2006; 17 ( ): 339-48.

Reznikov AG, Chaykovskaya LV, Polyakova LI, Kornelyuk AI. Antitumor effect of endothelial monocyte-activating polypeptide-II on human prostate adenocarcinoma in mouse xenograft model. Exp Oncol. 2007; 29( ): 267–71.

Schwarz RE1, Awasthi N, Konduri S, Cafasso D, Schwarz MA. EMAP II-based antiangiogenic-antiendothelial in vivo combination therapy of pancreatic cancer. Ann Surg Oncol. 2010; 17(5):1442-52.

Schwarz RE, Schwarz MA. In vivo therapy of local tumor progression by targeting vascular endhothelium with EMAP II. J Surg Res 2004; J Surg Res 2004; 120 ( ): 64–72.

Kolomiets-Babenko LA, Bohorad-Kobelska OS, Kovalchuk NL, Spivak MJ, Kornelyuk AI. Nanocomposite complex EMAP II influence on tumor necrosis factor and interferon in vitro. Biotechnologia Acta. 2016; 9 (5):

Babenko LA, Skorobogatov OY, Dubrovsky OL, Kornelyuk OI. Bacterial expression optimization of EMAP II antitumor cytokine in E.coli BL21(DE3)pLys. Microbiology and Biotechnology. 2010; 3 ( ): 21-31.

Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227 (5259): 680-685

T.A. Goloborodko, L.I. Polyakova, A.V. Sotkis, A.I. Korneliuk, L.A. Babenko, Ya.M. Shuba, A.G. Reznikov. Polypeptide EMAP II inhibits growth and stimulates apoptosis of the LnCaP prostate cancer cell line J.of the Nation Academy of Medical Sciences of Ukraine.2010; 16(4): 681-690.

Received in the editorial: 03.10.2018

Received a revised version: 04.10.2018

Signed in the press: 04.10.2018


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