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Methionine gamma lyase from Clostridium sporogenes increases the anticancer effect of doxorubicin in A549 cells and human cancer xenografts

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Summary

The anti-cancer efficacy of methionine γ-lyase (MGL) from Clostridium sporogenes (C. sporogenes) is described. MGL was active against cancer models in vitro and in vivo. The calculated EC50 values for MGL were 4.4 U/ml for A549, 7.5 U/ml for SK-BR3, 2.4 U/ml for SKOV3, and 0.4 U/ml for MCF7 cells. The combination of doxorubicin (DOX) and MGL was more effective for A549 human lung cancer growth inhibition than either agent alone in vitro and in vivo. MGL reduced the EC50 of doxorubicin from 35.9 μg/mL to 0.01–0.265 μg/mL. The growth inhibitory effect of DOX + MGL on A549 xenografts in vivo was reflective of the results obtained in vitro. The inhibition rate of tumor growth in the combined arm was 57%, significantly higher than that in the doxorubicin (p = 0.033)-alone arm.

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Acknowledgements

The authors thank Prof. Robert Hoffman (AntiCancer Inc., San Diego, USA) and Prof. Tatiana Demidkina (Engelhardt Institute of Molecular Biology, Moscow, Russia) for valuable comments and suggestions.

Funding

The publication has been prepared with the support of the “RUDN University program 5-100”, and research grant MD-1780.2017.7 from the presidential grant committee.

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Authors and Affiliations

  1. Laboratory of Combined Treatment, Laboratory of Cell Immunity, N.N. Blokhin Cancer Research Center, Moscow, Russia

    V. S. Pokrovsky, N. Yu Anisimova & D. Zh Davydov

  2. Department of Biochemistry, Peoples’ Friendship University of Russia (RUDN University), Moscow, Russia

    V. S. Pokrovsky

  3. State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow, Russia

    S. V. Bazhenov, N. V. Bulushova, G. B. Zavilgelsky, V. Y. Kotova & I. V. Manukhov

  4. Laboratory of Molecular Genetics, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow, Region, Russia

    S. V. Bazhenov & I. V. Manukhov

Authors
  1. V. S. Pokrovsky
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  2. N. Yu Anisimova
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  3. D. Zh Davydov
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  4. S. V. Bazhenov
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  5. N. V. Bulushova
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  6. G. B. Zavilgelsky
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  7. V. Y. Kotova
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  8. I. V. Manukhov
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Correspondence to V. S. Pokrovsky.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Pokrovsky, V.S., Yu Anisimova, N., Zh Davydov, D. et al. Methionine gamma lyase from Clostridium sporogenes increases the anticancer effect of doxorubicin in A549 cells and human cancer xenografts. Invest New Drugs 37, 201–209 (2019). https://doi.org/10.1007/s10637-018-0619-4

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  • DOI: https://doi.org/10.1007/s10637-018-0619-4

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