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Bulletin of Experimental Biology and Medicine

, Volume 166, Issue 5, pp 661–666 | Cite as

Antimetastatic Activity of Combined Topotecan and Tyrosyl-DNA Phosphodiesterase-1 Inhibitor on Modeled Lewis Lung Carcinoma

  • E. V. KoldyshevaEmail author
  • A. P. Men’shchikova
  • E. L. Lushnikova
  • N. A. Popova
  • V. I. Kaledin
  • V. P. Nikolin
  • A. L. Zakharenko
  • O. A. Luzina
  • N. F. Salakhutdinov
  • O. I. Lavrik
Article
  • 22 Downloads

The antimetastatic activity of combined or individual administration of topotecan and tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitor was examined under various administration schedules in mice with Lewis lung carcinoma modeled by intravenous injection of 200,000 clone/mouse. The greatest antimetastatic effect was observed after combined use of topotecan and Tdp1 inhibitor as documented by macroscopic study of the lungs that revealed the decreased metastatic scores by 76, 91, or 74% at the respective inhibitor doses of 2, 4, or 6 mg/mouse, respectively, in parallel with inhibition of metastasis up to 98% (at inhibitor dose of 4 mg/mouse) and morphological and morphometric analyses of the lung sections, which revealed elevation of metastasis growth delay index to 86 and 63% at the respective inhibitor doses of 4 and 6 mg/mouse, respectively. The combined administration of topotecan and Tdp1 inhibitor is viewed as the most effective way to eliminate the metastatic formations with possible restitution of focal lesions.

Key Words

Lewis lung carcinoma metastases topotecan tyrosyl-DNA phosphodiesterase-1 inhibitor morphometry 

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References

  1. 1.
    Avtandilov GG. Diagnostic Medical Morphometry. Moscow, 2002. Russian.Google Scholar
  2. 2.
    Buldakov МА, Litviakov NV, Klimov IА, Kutenkov OP, Bolshakov МА, Rostov VV, Cherdyntseva NV. Low-dose repetitively-pulsed x-ray influence on Lewis lung carcinoma growth and metastasis. Sib. Onkol. Zh. 2011;(6):47-51. Russian.Google Scholar
  3. 3.
    Bychkov MB, Gorbunova VA. Clinical Guidelines on Diagnosis and Treatment of Patients with Lung Carcinomas. Moscow, 2014. Russian.Google Scholar
  4. 4.
    Zakharenko AL, Lebedeva NA, Lavrik OI. DNA Repair Enzymes as Promising Targets in Oncotherapy. Russ. J. Bioorgan. Chem. 2018;44(1):1-18.Google Scholar
  5. 5.
    Zakharenko AL, Rechkunova NI, Lavrik OI. Inhibitors of DNA repair enzymes as prototypes of medicinal preparations. Vopr. Biol., Med., Farm. Khimii. 2015;(3):26-34. Russian.Google Scholar
  6. 6.
    Luzina OA, Salakhutdinov NF. Biological activity of usnic acid and its derivatives: Part 2. effects on higher organisms. Molecular and physicochemical aspects. Russ. J. Bioorgan. Chem. 2016;42(3):249-268.Google Scholar
  7. 7.
    Sorokina IV, Tolstikova TG, Zhukova NA, Petrenko NI, Uzenkova NV, Shul’ts EE, Popova NA. Antitumor and antimetastatic effects of betulonic acid amides in mice with transplantable Lewis carcinoma. Bull. Exp. Biol. Med. 2006;142(1):69-72.Google Scholar
  8. 8.
    Tatyanenko LV, Konovalova NP, Bogdanov GN, Dobrokhotova ОV, Fedorov BS. Inhibition of active transport of calcium ions by PT(IV) and PD(II) metal complexes. Correlation between the process and the inhibition of growth of experimental metastases. Biomed. Khimiya. 2006;52(1):52-59. Russian.Google Scholar
  9. 9.
    Alagoz M, Gilbert DC, El-Khamisy S, Chalmers AJ. DNA repair and resistance to topoisomerase I inhibitors: mechanisms, biomarkers and therapeutic targets. Curr. Med. Chem. 2012;19(23):3874-3885.Google Scholar
  10. 10.
    Barthelmes HU, Habermeyer M, Christensen MO, Mielke C, Interthal H, Pouliot JJ, Boege F, Marko D. TDP1 overexpression in human cells counteracts DNA damage mediated by topoisomerases I and II. J. Biol. Chem. 2004;279(53):55 618-55 625.Google Scholar
  11. 11.
    Beretta GL, Cossa G, Gatti L, Zunino F, Perego P. Tyrosyl-DNA phosphodiesterase 1 targeting for modulation of camptothecin-based treatment. Curr. Med. Chem. 2010;17(15):1500-1508.Google Scholar
  12. 12.
    Comeaux EQ, van Waardenburg RC. Tyrosyl-DNA phosphodiesterase 1 resolves both naturally and chemically induced DNA adducts and its potential as a therapeutic target. Drug Metab. Rev. 2014;46(4):494-507.Google Scholar
  13. 13.
    Huang HC, Liu J, Baglo Y, Rizvi I, Anbil S, Pigula M, Hasan T. Mechanism-informed repurposing of minocycline overcomes resistance to topoisomerase inhibition for peritoneal carcinomatosis. Mol. Cancer Ther. 2018;17(2):508-520.Google Scholar
  14. 14.
    Nivens MC, Felder T, Galloway AH, Pena MM, Pouliot JJ, Spencer HT. Engineered resistance to camptothecin and antifolates by retroviral coexpression of tyrosyl DNA phosphodiesterase-I and thymidylate synthase. Cancer Chemother. Pharmacol. 2004;53(2):107-115.Google Scholar
  15. 15.
    Zakharenko A, Luzina O, Koval O, Nilov D, Gushchina I, Dyrkheeva N, Švedas V, Salakhutdinov N, Lavrik O. Tyrosyl-DNA phosphodiesterase 1 inhibitors: usnic acid enamines enhance the cytotoxic effect of camptothecin. J. Nat. Prod. 2016;79(11):2961-2967.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • E. V. Koldysheva
    • 1
    Email author
  • A. P. Men’shchikova
    • 5
  • E. L. Lushnikova
    • 1
  • N. A. Popova
    • 2
    • 5
  • V. I. Kaledin
    • 2
  • V. P. Nikolin
    • 2
  • A. L. Zakharenko
    • 3
  • O. A. Luzina
    • 4
  • N. F. Salakhutdinov
    • 4
    • 5
  • O. I. Lavrik
    • 3
    • 5
  1. 1.Institute of Molecular Pathology and PathomorphologyFederal Research Center of Fundamental and Translational MedicineNovosibirskRussia
  2. 2.Federal Research Center Institute of Cytology and GeneticsSiberian Division of the Russian Academy of SciencesNovosibirskRussia
  3. 3.Institute of Chemical Biology and Fundamental MedicineSiberian Division of the Russian Academy of SciencesNovosibirskRussia
  4. 4.N. N. Vorozhtsov Novosibirsk Institute of Organic ChemistrySiberian Division of the Russian Academy of SciencesNovosibirskRussia
  5. 5.Novosibirsk National Research State UniversityNovosibirskRussia

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