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Comparative Analysis of Cytotoxic Activity of New Nitrosyl Iron—Sulfur Complexes in Human Tumor Cells In Vitro

  • Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

We studied cytotoxic activity of new tetranitrosyl NO-generating binuclear iron—sulfur [Fe—S] complexes containing different ligands in the molecule against tumor cells in vitro. Cytotoxic activity of the most active complex with cysteamine (CysAm) was compared with that of antitumor drug cisplatin. Caspase activation and morphological changes in cells were visualized by fluorescence microscopy. Fluorescence of active caspases 3 and 7 and changes in nuclear DNA in cells in the presence of CyAm were detected by using fluorochrome-labeled inhibitor of caspases (FLICA) and Hoechst and propidium iodide reagents. Similar cytotoxic activities of CyAm and cisplatin were demonstrated in various human tumor cell lines of different histogenesis. Therefore, a new class of NO-donating [Fe—S] complexes can provide the base of potential drugs for chemotherapy with a new mechanism of action.

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References

  1. Voitkova VV. Study of apoptosis with use of flow cytometry (review of literature). Byull. Vost.-Sib. Nauch. Tsentra Sib. Otdel. Ross. Akad. Med. Nauk. 2010;(6-1):220-225. Russian.

  2. Zhukova OS. In vitro models in screening of different nature antitumor compounds. Ross. Bioter. Zh. 2004;3(3):12-18. Russian.

  3. Makarov MS. Fluorescence in cell research: approaches and possibilities. Mol. Med. 2013;(4):10-14. Russian.

  4. Treshchalina EM, Zhukova OS, Gerasimova GK, Andronova NV, Garin AM. Methodical recommendations on preclinical evaluation of antitumor activity of drugs. Manual for Preclinical Studies of Drugs. Part I. Mironov AN, ed. Moscow, 2013. P. 642-656. Russian.

  5. Boulikas T, Vougiouka M. Cisplatin and platinum drugs at the molecular level. (Review). Oncol. Rep. 2003;10(6):1663-1682.

    CAS  Google Scholar 

  6. Brozovic A, Ambriović-Ristov A, Osmak M. The relationship between cisplatin-induced reactive oxygen species, glutathione, and BCL-2 and resistance to cisplatin. Crit. Rev. Toxicol. 2010;40(4):347-359.

    Article  CAS  Google Scholar 

  7. Chian S, Li. YY, Wang XJ, Tang XW. Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway. Asian Pac. J. Cancer Prev. 2014;15(6):2911-2916.

    Google Scholar 

  8. Cho JM, Manandhar S, Lee HR, Park HM, Kwak MK. Role of the Nrf2-antioxidant system in cytotoxicity mediated by anticancer cisplatin: implication to cancer cell resistance. Cancer Lett. 2008;260(1-2):96-108.

    Article  CAS  Google Scholar 

  9. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur. J. Pharmacol. 2014;740:364-378.

    Article  CAS  Google Scholar 

  10. Frezza M, Hindo S, Chen D, Davenport A, Schmitt S, Tomco D, Dou Q.P. Novel metals and metal complexes as platforms for cancer therapy. Curr. Pharm. Des. 2010;16(16):1813-1825.

    Article  CAS  Google Scholar 

  11. Haglund C, Aleskog A, Nygren P, Gullbo J, Höglund M, Wickström M, Larsson R, Lindhagen E. In vitro evaluation of clinical activity and toxicity of anticancer drugs using tumor cells from patients and cells representing normal tissues. Cancer Chemother. Pharmacol. 2012;69(3):697-707.

    Article  CAS  Google Scholar 

  12. Holzer AK, Manorek GH, Howell SB. Contribution of the major copper influx transporter CTR1 to the cellular accumulation of cisplatin, carboplatin, and oxaliplatin. Mol. Pharmacol. 2006;70(4):1390-1394.

    Article  CAS  Google Scholar 

  13. Isono S, Fujishima M, Azumi T, Hashimoto Y, Komoike Y, Yukawa M, Watatani M. O6-methylguanine-DNA methyltransferase as a prognostic and predictive marker for basal-like breast cancer treated with cyclophosphamide-based chemotherapy. Oncol. Lett. 2014;7(6):1778-1784.

    Article  CAS  Google Scholar 

  14. Jia J, Zhu F, Ma X, Cao Z, Cao ZW, Li Y, Li YX, Chen YZ. Mechanisms of drug combinations: interaction and network perspectives. Nat. Rev. Drug Discov. 2009;8(2):111-128.

    Article  CAS  Google Scholar 

  15. Johnstone TC, Wilson JJ, Lippard SJ. Monofunctional and higher-valent platinum anticancer agents. Inorg. Chem. 2013; 52(21):12,234-12,249.

    Article  CAS  Google Scholar 

  16. Kielbik M, Klink M, Brzezinska M, Szulc I, Sulowska Z. Nitric oxide donors: spermine/NO and diethylenetriamine/NO induce ovarian cancer cell death and affect STAT3 and AKT signaling proteins. Nitric Oxide. 2013;35:93-109.

    Article  CAS  Google Scholar 

  17. Lee BW, Olin MR, Johnson GL, Griffin RJ. In vitro and in vivo apoptosis detection using membrane permeant fluorescent-labeled inhibitors of caspases. Methods Mol. Biol. 2008;414:109-135.

    CAS  PubMed  Google Scholar 

  18. Ostrowski AD, Ford PC. Metal complexes as photochemical nitric oxide precursors: potential applications in the treatment of tumors. Dalton Trans. 2009;(48):10,660-10,669.

    Article  Google Scholar 

  19. Pop C, Salvesen GS. Human caspases: activation, specificity, and regulation. J. Biol. Chem. 2009;284(33):21,777-21,781.

    Article  CAS  Google Scholar 

  20. Sanina NA, Rudneva TN, Aldoshin SM, Shilov GV, Kortchagin DV, Shul’ga YuM, Martynenko VM, Ovanesyan NS. Influence of CH3 group of μ-N-C-S ligand on the properties of [FE2(C4H5N2S)2(NO)4] complex. Inorg. Chem. Acta. 2006;359(2):570-576.

    Article  CAS  Google Scholar 

  21. Sanina NA, Kozub GI, Emelyanova NS, Kondrateva TA, Korchagin DV, Shilov GV, Ovanesyan NS, Aldoshin SM, Zhukova OS. Synthesis, structure, no donor activity of iron-sulfur nitrosyl complex with 2-aminophenol-2-yl and its antiproliferative activity against human cancer cells. J. Coordinat. Chem. 2013;66(20):3602-3618.

    Article  CAS  Google Scholar 

  22. Serafim RA, Primi MC, Trossini GH, Ferreira EI. Nitric oxide: state of the art in drug design. Curr. Med. Chem. 2012;19(3):386-405.

    Article  CAS  Google Scholar 

  23. Shen DW, Liang XJ, Suzuki T, Gottesman MM. Identification by functional cloning from a retroviral cDNA library of cDNAs for ribosomal protein L36 and the 10-kDa heat shock protein that confer cisplatin resistance. Mol. Pharmacol. 2006;69(4):1383-1388.

    Article  CAS  Google Scholar 

  24. Smith L, Welham KJ, Watson MB, Drew PJ, Lind MJ, Cawkwell L. The proteomic analysis of cisplatin resistance in breast cancer cells. Oncol. Res. 2007;16(11):497-506.

    Article  CAS  Google Scholar 

  25. Takimoto CH. Anticancer drug development at the US National Cancer Institute. Cancer. Chemother. Pharmacol. 2003;52(Suppl.1):S29-S33.

    Article  CAS  Google Scholar 

  26. Tesei A, Zoli W, Fabbri F, Leonetti C, Rosetti M, Bolla M, Amadori D, Silvestrini R. NCX 4040, an NO-donating acetylsalicylic acid derivative: efficacy and mechanisms of action in cancer cells. Nitric Oxide. 2008;19(2):225-236.

    Article  CAS  Google Scholar 

  27. Zhukova OS, Smirnova ZS, Chikileva IO, Kiselevskii MV. Antiproliferative activity of a new nitrosyl iron complex with cysteamine in human tumor cells in vitro. Bull. Exp. Biol. Med. 2017;162(4):583-588.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Cell Immunology, Moscow, Russia

    O. S. Zhukova, M. V. Kiselevskii, L. V. Fetisova & N. V. Malakhova

  2. Laboratory of Experimental Chemotherapy, N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, Russia

    L. M. Borisova & M. P. Kiseleva

Authors
  1. O. S. Zhukova
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  2. M. V. Kiselevskii
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  3. L. V. Fetisova
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  4. L. M. Borisova
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  5. N. V. Malakhova
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  6. M. P. Kiseleva
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Correspondence to O. S. Zhukova.

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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 1, pp. 12-19, January, 2020

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Zhukova, O.S., Kiselevskii, M.V., Fetisova, L.V. et al. Comparative Analysis of Cytotoxic Activity of New Nitrosyl Iron—Sulfur Complexes in Human Tumor Cells In Vitro. Bull Exp Biol Med 169, 130–136 (2020). https://doi.org/10.1007/s10517-020-04839-0

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  • DOI: https://doi.org/10.1007/s10517-020-04839-0

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