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Interceptor effect of C60 fullerene on the in vitro action of aromatic drug molecules

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Abstract

C60 fullerenes are spherical molecules composed purely of carbon atoms. They inspire a particularly strong scientific interest because of their specific physico-chemical properties and potential medical and nanotechnological applications. In this work we are focusing on studying the influence of the pristine C60 fullerene on biological activity of some aromatic drug molecules in human buccal epithelial cells. Assessment of the heterochromatin structure in the cell nucleus as well as the barrier function of the cell membrane was performed. The methods of cell microelectrophoresis and atomic force microscopy were also applied. A concentration-dependent restoration of the functional activity of the cellular nucleus after exposure to DNA-binding drugs (doxorubicin, proflavine and ethidium bromide) has been observed in human buccal epithelial cells upon addition of C60 fullerene at a concentration of ~10−5 M. The results were shown to follow the framework of interceptor/protector action theory, assuming that non-covalent complexation between C60 fullerene and the drugs (i.e., hetero-association) is the major process responsible for the observed biological effects. An independent confirmation of this hypothesis was obtained via investigation of the cellular response of buccal epithelium to the coadministration of the aromatic drugs and caffeine, and it is based on the well-established role of hetero-association in drug-caffeine systems. The results indicate that C60 fullerene may reverse the effects caused by the aromatic drugs, thereby pointing out the potential possibility of the use of aromatic drugs in combination with C60 fullerene for regulation of their medico-biological action.

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References

  • Andrievsky G, Klochkov V, Derevyanchenko L (2005) Is the C60 fullerene molecule toxic?! Fuller Nanotub Carbon Nanostr 13(4):363–376

    Article  CAS  Google Scholar 

  • Anilkumar P, Lu F, Cao L et al (2011) Fullerenes for applications in biology and medicine. Curr Med Chem 18(14):2045–2059

    CAS  PubMed  Google Scholar 

  • Aschberger K, Johnston HJ, Stone V et al (2010) Review of fullerene toxicity and exposure—appraisal of a human health risk assessment, based on open literature. Regul Toxicol Pharmacol 58(3):455–473

    Article  CAS  PubMed  Google Scholar 

  • Buchelnikov AS, Santiago AH, Flores MG, Ramirez RV, Davies D, Evstigneev M (2012) General analysis of competitive binding in drug–interceptor–DNA systems. Eur Biophys J 41(3):273–283

    Article  CAS  PubMed  Google Scholar 

  • Buchelnikov A, Kostyukov V, Yevstigneev M, Prylutskyy YI (2013) Mechanism of complexation of the phenothiazine dye methylene blue with fullerene C60. Russ J Phys Chem A 87(4):662–667

    Article  CAS  Google Scholar 

  • Bulavin L, Adamenko I, Prylutskyy Y et al (2000) Structure of fullerene C60 in aqueous solution. Phys Chem Chem Phys 2(8):1627–1629

    Article  CAS  Google Scholar 

  • Cataldo F, Da Ros T (2008) Medicinal chemistry and pharmacological potential of fullerenes and carbon nanotubes. Springer, Netherlands

    Book  Google Scholar 

  • Evstigneev MP (2010) DNA-binding aromatic drug molecules: physico-chemical interactions and their biological roles. LAP. ISBN 978-3-8433-5389-2

  • Evstigneev MP (2013) Physicochemical mechanisms of synergistic biological action of combinations of aromatic heterocyclic compounds. Org Chem Int. doi:10.1155/2013/278143

  • Evstigneev M, Khomich V, Davies D (2006) Complexation of anthracycline drugs with DNA in the presence of caffeine. Eur Biophys J 36(1):1–11

    Article  CAS  PubMed  Google Scholar 

  • Evstigneev M, Lantushenko A, Evstigneev V, Mykhina YV, Davies D (2008) Quantitation of the molecular mechanisms of biological synergism in a mixture of DNA-acting aromatic drugs. Biophys Chem 132(2):148–158

    Article  CAS  PubMed  Google Scholar 

  • Evstigneev M, Mosunov A, Evstigneev V, Parkes H, Davies D (2011) Quantification of the interceptor action of caffeine on the in vitro biological effect of the anti-tumour agent topotecan. Eur Biophys J 40(8):969–980

    Article  CAS  PubMed  Google Scholar 

  • Evstigneev MP, Buchelnikov AS, Voronin DP et al (2013) Complexation of C60 fullerene with aromatic drugs. Chem Phys Chem 14(3):568–578

    Article  CAS  PubMed  Google Scholar 

  • Foley S, Crowley C, Smaihi M et al (2002) Cellular localisation of a water-soluble fullerene derivative. Biochem Biophys Res Commun 294(1):116–119

    Article  CAS  PubMed  Google Scholar 

  • Gołuński G, Woziwodzka A, Iermak I, Rychłowski M, Piosik J (2013) Modulation of acridine mutagen ICR191 intercalation to DNA by methylxanthines—analysis with mathematical models. Bioorg Med Chem 21:3280–3289

    Article  PubMed  Google Scholar 

  • Kolosnjaj J, Szwarc H, Moussa F (2007) Toxicity studies of fullerenes and derivatives. Bio-applications of nanoparticles, Landes Bioscience and Springer Science, pp 168–180

  • Larsen RW, Jasuja R, Hetzler RK, Muraoka PT, Andrada VG, Jameson DM (1996) Spectroscopic and molecular modeling studies of caffeine complexes with DNA intercalators. Biophys J 70(1):443–452

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Martin RM, Cardoso MC (2010) Chromatin condensation modulates access and binding of nuclear proteins. FASEB J 24:1066–1072

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mchedlov-Petrossyan N, Klochkov V, Andrievsky G, Ishchenko A (2001) Interaction between colloidal particles of C60 hydrosol and cationic dyes. Chem Phys Lett 341(3):237–244

    Article  CAS  Google Scholar 

  • Piosik J, Wasielewski K, Woziwodzka A, Śledź W, Gwizdek-Wiśniewska A (2010) De-intercalation of ethidium bromide and propidium iodine from DNA in the presence of caffeine. Central Eur J Biol 5(1):59–66

    Article  CAS  Google Scholar 

  • Prilutskyy YI, Durov S, Yashchuk V et al (1999) Theoretical predictions and experimental studies of self-organized C60 nanoparticles in water solution and on the support. Eur Phys J D Atomic Mol Opt Plasma Phys 9(1):341–343

    Google Scholar 

  • Prylutska S, Matyshevska O, Golub A et al (2007a) Study of C60 fullerenes and C60-containing composites cytotoxicity in vitro. Mater Sci Eng 27(5–8):1121–1124

    Article  CAS  Google Scholar 

  • Prylutska S, Matyshevska O, Grynyuk I, Prylutskyy YI, Ritter U, Scharff P (2007b) Biological effects of C60 fullerenes in vitro and in a model system. Mol Cryst Liq Cryst 468(1):265–274

    Article  Google Scholar 

  • Prylutska S, Grynyuk I, Matyshevska O, Prylutskyy YI, Ritter U, Scharff P (2008) Anti-oxidant properties of C60 fullerenes in vitro. Fuller Nanotub Carbon Nanostr 16(5–6):698–705

    Article  CAS  Google Scholar 

  • Prylutska S, Burlaka A, Prylutskyy YI, Ritter U, Scharff P (2011a) Pristine C60 fullerenes inhibit the rate of tumor growth and metastasis. Exp Oncol 33:162–164

    CAS  PubMed  Google Scholar 

  • Prylutska S, Burlaka A, Klymenko P et al (2011b) Using water-soluble C60 fullerenes in anticancer therapy. Cancer Nanotechnol 2(1–6):105–110

    Article  CAS  Google Scholar 

  • Prylutska S, Burlaka A, Prylutskyy YI (2011c) Comparative study of antitumor effect of pristine C60 fullerenes and doxorubicin. Biotechnol 4(6):82–87

    Google Scholar 

  • Prylutska S, Bilyy R, Overchuk M et al (2012) Water-soluble pristine fullerenes C60 increase the specific conductivity and capacity of lipid model membrane and form the channels in cellular plasma membrane. J Biomed Nanotechnol 8(3):522–527

    Article  CAS  PubMed  Google Scholar 

  • Prylutskyy YI, Durov S, Bulavin L et al (2001) Structure and thermophysical properties of fullerene C60 aqueous solutions. Int J Thermophys 22(3):943–956

    Article  CAS  Google Scholar 

  • Prylutskyy YI, Buchelnikov AS, Voronin DP et al (2013) C60 fullerene aggregation in aqueous solution. Phys Chem Chem Phys 15(23):9351–9360

    Article  CAS  PubMed  Google Scholar 

  • Qiao R, Roberts AP, Mount AS, Klaine SJ, Ke PC (2007) Translocation of C60 and its derivatives across a lipid bilayer. Nano Lett 7(3):614–619

    Article  CAS  PubMed  Google Scholar 

  • Scharff P, Risch K, Carta-Abelmann L et al (2004) Structure of C60 fullerene in water: spectroscopic data. Carbon 42(5):1203–1206

    Article  CAS  Google Scholar 

  • Shckorbatov YG, Shakhbazov VG, Bogoslavsky AM, Rudenko AO (1995) On age-related changes of cell membrane permeability in human buccal epithelium cells. Mech Ageing Dev 83(2):87–90

    Article  CAS  PubMed  Google Scholar 

  • Shckorbatov YG, Shakhbazov VG, Gorenskaya OV (1998) The effect of hormones on the electrokinetic properties of the nuclei of human cells. L’Eurobiol 32(234):172

    Google Scholar 

  • Shckorbatov YG, Shakhbazov VG, Navrotskaya VV et al (2002) Application of intracellular microelectrophoresis to analysis of the influence of the low-level microwave radiation on electrokinetic properties of nuclei in human epithelial cells. Electrophoresis 23(13):2074–2079

    Article  CAS  PubMed  Google Scholar 

  • Shckorbatov Y, Pasiuga V, Kolchigin N, Batrakov D, Kazansky O, Kalashnikov V (2009a) Changes in the human nuclear chromatin induced by ultra wideband pulse irradiation. Central Eur J Biol 4(1):97–106

    Article  Google Scholar 

  • Shckorbatov YG, Pasiuga VN, Kolchigin NN et al (2009b) The influence of differently polarised microwave radiation on chromatin in human cells. Int J Radiat Biol 85(4):322–329

    Article  CAS  PubMed  Google Scholar 

  • Traganos F, Kapuscinski J, Darzynkiewicz Z (1991) Caffeine modulates the effects of DNA-intercalating drugs in vitro: a flow cytometric and spectrophotometric analysis of caffeine interaction with novantrone, doxorubicin, ellipticine, and the doxorubicin analogue AD198. Cancer Res 51(14):3682–3689

    CAS  PubMed  Google Scholar 

  • Woziwodzka A, Gwizdek-Wiśniewska A, Piosik J (2011) Caffeine, pentoxifylline and theophylline form stacking complexes with IQ-type heterocyclic aromatic amines. Bioorg Chem 39(1):10–17

    Article  CAS  PubMed  Google Scholar 

  • Woziwodzka A, Gołuński G, Piosik J (2013) Heterocyclic aromatic amines heterocomplexation with biologically active aromatic compounds and its possible role in chemoprevention. ISRN Biophys 740821:11. doi:10.1155/2013/740821

    Google Scholar 

  • Zhao X, Striolo A, Cummings PT (2005) C60 binds to and deforms nucleotides. Biophys J 89(6):3856–3862

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

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Correspondence to Maxim P. Evstigneev.

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Skamrova, G.B., Laponogov, I., Buchelnikov, A.S. et al. Interceptor effect of C60 fullerene on the in vitro action of aromatic drug molecules. Eur Biophys J 43, 265–276 (2014). https://doi.org/10.1007/s00249-014-0960-2

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  • DOI: https://doi.org/10.1007/s00249-014-0960-2

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