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In vitro effects of a new fused azaisocytosine-like congener on relative cell proliferation, necrosis and cell cycle in cancer and normal cell cultures

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Abstract

The study was aimed at describing the mode of action of an innovative drug-like congener of fused azaisocytosine—EIMTC (ethyl 8-(4-methoxyphenyl)-4-oxo-6,7-dihydroimidazo[2,1-c][1,2,4]triazine-3-carboxylate)—on cancer cells in early in vitro oncology-related bioassays. Micromolar concentrations of EIMTC were effective at inhibiting the growth of two types of malignant multiple myeloma cells (including cells resistant to thalidomide) while having less cytotoxic effect on normal HSF cells. Furthermore, EIMTC was disclosed as capable of producing the statistically significant decrease in the number of cells in the S phase (in HeLa, TOV112D, T47D and Vero cells) and in the G2/M phase (in TOV112D cells) as well as evoking the distinctly higher necrosis rates in malignant than normal cells of the same epithelial origin. These results are promising in the sense that the bicyclic nucleobase-like structure related to azaisocytosine may target epithelial cancer cells and inhibit their growth while having less effect on normal cells. This may be due to induction of necrosis.

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Acknowledgments

Authors gratefully acknowledged Dr. Katarzyna Skórzyńska (Medical University of Lublin, Poland) for the generous gifts of MM1R and MM1S cell lines.

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Authors and Affiliations

  1. Chair and Department of Medical Chemistry, Medical University, 4A Chodźki Street, 20-093, Lublin, Poland

    Małgorzata Sztanke

  2. Department of Biology and Genetics, Medical University, 4A Chodźki Street, 20-093, Lublin, Poland

    Jolanta Rzymowska

  3. Laboratory of Bioorganic Synthesis and Analysis, Chair and Department of Medical Chemistry, Medical University, 4A Chodźki Street, 20-093, Lublin, Poland

    Krzysztof Sztanke

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  1. Małgorzata Sztanke
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  2. Jolanta Rzymowska
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  3. Krzysztof Sztanke
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Correspondence to Małgorzata Sztanke.

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Sztanke, M., Rzymowska, J. & Sztanke, K. In vitro effects of a new fused azaisocytosine-like congener on relative cell proliferation, necrosis and cell cycle in cancer and normal cell cultures. Mol Cell Biochem 418, 179–188 (2016). https://doi.org/10.1007/s11010-016-2744-8

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