Skip to main content
SpringerLink
Log in

In situ electrochemical evaluation of anticancer drug temozolomide and its metabolites–DNA interaction

  • Original Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Temozolomide (TMZ) is an antineoplastic alkylating agent with activity against serious and aggressive types of brain tumours. It has been postulated that TMZ exerts its antitumor activity via its spontaneous degradation at physiological pH. The in vitro evaluation of the interaction of TMZ and its final metabolites, 5-aminoimidazole-4-carboxamide (AIC) and methyldiazonium ion, with double-stranded DNA (dsDNA) was studied using differential pulse voltammetry at a glassy carbon electrode. The DNA damage was electrochemically detected following the changes in the oxidation peaks of guanosine and adenosine residues. The results obtained revealed the decrease of the dsDNA oxidation peaks with incubation time, showing that TMZ and AIC/methyldiazonium ion interact with dsDNA causing its condensation. Furthermore, the experiments of the in situ TMZ and AIC/methyldiazonium ion–dsDNA interaction using the multilayer dsDNA-electrochemical biosensor confirmed the condensation of dsDNA caused by these species and showed evidence for a specific interaction between the guanosine residues and TMZ metabolites, since free guanine oxidation peak was detected. The oxidative damage caused to DNA bases by TMZ metabolites was also detected electrochemically by monitoring the appearance of the 8-oxoguanine/2,8-dyhydroxyadenine oxidation peaks. Nondenaturing agarose gel electrophoresis of AIC/methyldiazonium ion–dsDNA samples confirmed the occurrence of dsDNA condensation and oxidative damage observed in the electrochemical results. The importance of the dsDNA-electrochemical biosensor in the in situ evaluation of TMZ–dsDNA interactions is clearly demonstrated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Marchesi F, Turriziani M, Tortorelli G, Avvisati G, Torino F, De Vecchis L (2007) Pharmacol Res 56:275–287

    Article  CAS  Google Scholar 

  2. Chaney SG, Sancar A (1996) J Natl Cancer Inst 88:1346–1360

    Article  CAS  Google Scholar 

  3. Stevens MF, Hickman JA, Stone R, Gibson NW, Baig GU, Lunt E, Newton CG (1984) J Med Chem 27:196–201

    Article  CAS  Google Scholar 

  4. Darkes MJM, Plosker GL, Jarvis B (2002) Am J Cancer 1:55–80

    Article  CAS  Google Scholar 

  5. Baker SD, Wirth M, Statkevich P, Reidenberg P, Alton K, Sartorius SE, Dugan M, Cutler D, Batra V, Grochow LB, Donehower RC, Rowinsky EK (1999) Clin Cancer Res 5:309–317

    CAS  Google Scholar 

  6. Yung WK, Prados MD, Yaya-Tur R, Rosenfeld SS, Brada M, Friedman HS, Albright R, Olson J, Chang SM, O’Neill AM, Friedman AH, Bruner J, Yue N, Dugan M, Zaknoen S, Levin VA (1999) J Clin Oncol 17:2762–2771

    CAS  Google Scholar 

  7. Pacia A, Rieutorda A, Brion F, Prognon P (2001) J Chromatogr B 764:255–287

    Article  Google Scholar 

  8. Chalmers AJ, Ruff EM, Martindale C, Lovegrove N, Short SC (2009) Int J Radiat Oncol 75:1511–1519

    Article  CAS  Google Scholar 

  9. Kondo N, Takahashi A, Mori E, Ohnishi K, McKinnon PJ, Sakaki T, Nakase H, Ohnishi T (2009) Biochem Biophys Res Commun 387:656–660

    Article  CAS  Google Scholar 

  10. Wang Y, Liu L, Wu C, Bulgar A, Somoza E, Zhu W, Gerson SL (2009) Nucl Med Biol 36:975–983

    Article  CAS  Google Scholar 

  11. Cui B, Johnson SP, Bullock N, Ali-Osman F, Bigner DD, Friedman HS (2010) J Biomed Res 24:424–435

    Article  CAS  Google Scholar 

  12. Britten CD, Rowinsky EK, Baker SD, Agarwala SS, Eckardt JR, Barrington R, Diab SG, Hammond LA, Johnson T, Villalona-Calero M, Fraass U, Statkevich P, Von Hoff DD, Eckhardt SG (1999) Clin Cancer Res 5:1629–1637

    CAS  Google Scholar 

  13. Park DM, Shah DD, Egorin MJ, Beumer JH (2009) J Neuro-Oncol 93:279–283

    Article  Google Scholar 

  14. Kim H, Likhari P, Parker D, Statkevich P, Marco A, Lin CC, Nomeir AA (2001) J Pharm Biomed Anal 24:461–468

    Article  CAS  Google Scholar 

  15. Andrasi M, Bustos R, Gaspar A, Gomez FA, Klekner A (2010) J Chromatogr B 878:1801–1808

    Article  CAS  Google Scholar 

  16. Kim HK, Lin CC, Parker D, Veals J, Lim J, Likhari P, Statkevich P, Marco A, Nomeir AA (1997) J Chromatogr B 703:225–233

    Article  CAS  Google Scholar 

  17. Diez BD, Statkevich P, Zhu Y, Abutarif MA, Xuan F, Kantesaria B, Cutler D, Cantillon M, Schwarz M, Pallotta MG, Ottaviano FH (2010) Cancer Chemother Pharmacol 65:727–734

    Article  CAS  Google Scholar 

  18. Taverna P, Liu L, Hwang H-S, Hanson AJ, Kinsella TJ, Gerson SL (2001) Mutat Res 485:269–281

    Article  CAS  Google Scholar 

  19. Passagne I, Evrard A, Depeille P, Cuq P, Cupissol D, Vian L (2006) Toxicol Appl Pharmacol 211:97–105

    Article  CAS  Google Scholar 

  20. Jakubowicz-Gil J, Langner E, Wertel I, Piersiak T, Rzeski W (2010) Chem Biol Interact 188:190–203

    Article  CAS  Google Scholar 

  21. Brett CMA, Oliveira-Brett AM (2003) In: Bard AJ, Stratmann M (eds) Encyclopedia of electrochemistry. Wiley-VCH, Weinheim

    Google Scholar 

  22. Oliveira SCB, Oliveira-Brett AM (2010) Comb Chem High Throuhput Screen 13:628–640

    Article  CAS  Google Scholar 

  23. Pontinha AD, Jorge SM, Chiorcea-Paquim AM, Diculescu VC, Oliveira-Brett AM (2011) Phys Chem Chem Phys 13:5227–5234

    Article  CAS  Google Scholar 

  24. Santos PVF, Lopes IC, Diculescu VC, Oliveira-Brett AM (2012) Electroanalysis 24:547–553

    Article  CAS  Google Scholar 

  25. Chiorcea-Paquim AM, Corduneanu O, Oliveira SCB, Diculescu VC, Oliveira-Brett AM (2009) Electrochim Acta 54:1978–1985

    Article  CAS  Google Scholar 

  26. Oliveira SCB, Oliveira-Brett AM (2010) Anal Bioanal Chem 398:1633–1641

    Article  CAS  Google Scholar 

  27. Oliveira SCB, Oliveira-Brett AM (2012) Langmuir 28(10):4896–4901

    Article  CAS  Google Scholar 

  28. Oliveira-Brett AM, da Silva LA, Brett CMA (2002) Langmuir 18:2326–2330

    Article  CAS  Google Scholar 

  29. Goyal RN, Sangal A (2002) J Electroanal Chem 521:72–80

    Article  CAS  Google Scholar 

  30. Ghalkhani M, Fernandes IPG, Oliveira SCB, Shahrokhian S, Oliveira-Brett AM (2010) Electroanalysis 22:2633–2640

    Article  CAS  Google Scholar 

  31. Rodriguez JRB, Garcia AC, Ordieres AJM, Blanco PT (1989) Electroanalysis 1:529–534

    Article  Google Scholar 

  32. Brody JR, Kern SE (2004) Anal Biochem 333:1–13

    Article  CAS  Google Scholar 

  33. Piedade JAP, Oliveira PSC, Lopes MC, Oliveira-Brett AM (2006) Anal Biochem 355:39–49

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Financial support from Fundação para a Ciência e Tecnologia (FCT), Post-Doctoral Grant SFRH/BPD/71965/2010 (S.C.B. Oliveira), project PTDC/QUI-QUI/098562/2008, POFC-QREN, POPH (co-financed by the European Community Funds FSE e FEDER/COMPETE), CEMUC-R (Research Unit 285), CNPq - Brazil, Post-Doctoral Grant/201487/2011-0 (I.C. Lopes) is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-535, Coimbra, Portugal

    Ilanna C. Lopes, S. Carlos B. Oliveira & Ana Maria Oliveira-Brett

Authors
  1. Ilanna C. Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Carlos B. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Maria Oliveira-Brett
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana Maria Oliveira-Brett.

Additional information

Published in the topical collection in Bioelectroanalysis with guest editors Nicolas Plumeré, Magdalena Gebala, and Wolfgang Schuhmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

C. Lopes, I., Oliveira, S.C.B. & Oliveira-Brett, A.M. In situ electrochemical evaluation of anticancer drug temozolomide and its metabolites–DNA interaction. Anal Bioanal Chem 405, 3783–3790 (2013). https://doi.org/10.1007/s00216-012-6546-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-012-6546-x

Keywords

Search

Navigation