Square‐Wave Voltammetry as a Tool for Investigation of Doxorubicin Interactions with DNA Isolated from Neuroblastoma Cells

Húska, Dalibor; Adam, Vojtěch; Babula, Petr; Hraběta, Jan; Stiborová, Marie; Eckschlager, Tomáš; Trnková, Libuše; Kizek, René

doi:10.1002/elan.200804429

Cited by 27 publications

(16 citation statements)

References 52 publications

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“…cesius inhibiting the synthesis of nucleic acids. They are commonly used in the treatment of a number of diverse malignant tumors -acute leukemia, non-Hodgkin's and Hodgkin's lymphoma and several solid tumors including neuroblastoma [57,[175][176][177][178]. On the other hand, the side effect of cumulative dose dependent cardiotoxicity, myelosuppression [179] as well as large distribution volume and low life time under physiological conditions [180] represent the limitations of its clinical use.…”

Section: Doxorubicinmentioning

confidence: 99%

Nanocarriers for Anticancer Drugs - New Trends in Nanomedicine

Drbohlavová

Chomoucká²,

Adam³

et al. 2013

CDM

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101

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This review provides a brief overview of the variety of carriers employed for targeted drug delivery used in cancer therapy and summarizes advantages and disadvantages of each approach. Particularly, the attention was paid to polymeric nanocarriers, liposomes, micelles, polyethylene glycol, poly(lactic-co-glycolic acid), dendrimers, gold and magnetic nanoparticles, quantum dots, silica nanoparticles, and carbon nanotubes. Further, this paper briefly focuses on several anticancer agents (paclitaxel, docetaxel, camptothecin, doxorubicin, daunorubicin, cisplatin, curcumin, and geldanamycin) and on the influence of their combination with nanoparticulate transporters to their properties such as cytotoxicity, short life time and/or solubility.

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Section: Doxorubicinmentioning

confidence: 99%

Nanocarriers for Anticancer Drugs - New Trends in Nanomedicine

Drbohlavová

Chomoucká²,

Adam³

et al. 2013

CDM

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101

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“…Their formation in neuroblastoma cells cannot, however, be excluded. Recently, changes in structure of DNA isolated from neuroblastoma cells induced by their treating with doxorubicin have been detected by square-wave voltammetry 38 . Nevertheless, whether these changes are produced by formation of actual covalent doxorubicinderived DNA adducts remain to be investigated.…”

Section: P-postlabelingmentioning

confidence: 99%

Analysis of covalent ellipticine- and doxorubicin-derived adducts in DNA of neuroblastoma cells by the <sup>32</sup>P-postlabeling technique

Stiborová¹,

Poljaková²,

Eckschlager³

et al. 2012

BIOMED PAP

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eBackground. Ellipticine and doxorubicin are antineoplastic agents, whose action is based mainly on DNA damage such as intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts. The key target to resolve which of these mechanisms are responsible for ellipticine and doxorubicin anticancer effects is the development of suitable methods for identifying their individual DNA-damaging effects. Here, the 32 P-postlabeling method was tested to detect covalent DNA adducts formed by ellipticine and doxorubicin. Methods. The standard procedure of 32 P-postlabeling assay, this procedure under ATP-deficient conditions, the version using extraction of adducts with n-butanol and the nuclease P1 enrichment version were used to analyze ellipticineand/or doxorubicin-derived DNA adducts. Results. Two covalent ellipticine-derived DNA adducts, which are associated with cytotoxicity of ellipticine to human UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines, were detected by the 32 P-postlabeling method. These adducts are identical to those formed by the ellipticine metabolites, 13-hydroxy-and 12-hydroxyellipticine. In contrast, no covalent adducts formed by doxorubicin in DNA of these neuroblastoma cells and in DNA incubated with this drug and formaldehyde in vitro were detectable by the 32 P-postlabeling assay. Conclusions. The results presented in this paper are the first to demonstrate that in contrast to covalent DNA adducts formed by ellipticine, the adducts generated by formaldehyde-mediated covalent binding of doxorubicin to DNA are not detectable by the 32 P-postlabeling assay. No DNA adducts were, detectable either in vitro, in incubations of DNA with doxorubicin or in DNA of neuroblastoma cells treated with this drug. The results also suggest that covalent binding of ellipticine to DNA of UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines is the predominant mechanism responsible for the cytotoxicity of this drug. To understand the mechanisms of doxorubicin anticancer effects on neuroblastoma cells, development of novel methods for identifying covalent doxorubicin-derived DNA adducts is the major challenge for further research.

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“…The elaborated mechanism in this work is especially relevant to study the chemistry between hydrophilic systems such as enzyme-substrates, drug-drug and drug-DNA interactions. [3,4,[20][21][22][23][24][25]…”

Section: Introductionmentioning

confidence: 99%

Diffusional Electrochemical Catalytic (EC’) Mechanism Featuring Chemical Reversibility of Regenerative Reaction-Theoretical Analysis in Cyclic Voltammetry

Petkovska

Gulaboski

2020

Croat. chem. acta (Online)

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We consider theoretically a specific electrochemical-catalytic mechanism associated with reversible regenerative chemical reaction, under conditions of cyclic staircase voltammetry (CSV). We suppose scenario in which two electrochemically inactive substrates “S” and “Y”, together with initial electrochemically active reactant Ox are present in voltammetric cell from the beginning of the experiment. Substrate “S” selectively reacts with initial electroactive reactant Ox and creates electroactive “product” Red (+ Y) in a reversible chemical fashion. The initial chemical equilibrium determines the amounts of Ox and Red available for electrode transformation at the beginning of the electrochemical experiment. Under conditions of applied potential, the electrode reaction Ox(aq) + ne– ⇋ Red(aq) occurs, producing flow of electric current. Under such circumstances, the chemical reaction coupled to the electrochemical step causes a regeneration of initial electroactive species during the time-frame of current-measuring segment in CSV. The features of cyclic voltammograms get significantly affected by the kinetics and thermodynamics of reversible regenerative reaction. We elaborate several aspects of this specific electrode mechanism, and we focus on the role of parameters related to chemical step to the features of calculated voltammograms. While we provide a specific set of results of this particular mechanism, we propose methods to get access to relevant kinetic and thermodynamic parameters relevant to regenerative chemical reaction. The results elaborated in this work can be valuable in evaluating kinetics of many drug-drug interactions, but they can be relevant to study interactions of many enzyme-substrate systems, as well.

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Square‐Wave Voltammetry as a Tool for Investigation of Doxorubicin Interactions with DNA Isolated from Neuroblastoma Cells

Cited by 27 publications

References 52 publications

Nanocarriers for Anticancer Drugs - New Trends in Nanomedicine

Nanocarriers for Anticancer Drugs - New Trends in Nanomedicine

Analysis of covalent ellipticine- and doxorubicin-derived adducts in DNA of neuroblastoma cells by the <sup>32</sup>P-postlabeling technique

Diffusional Electrochemical Catalytic (EC’) Mechanism Featuring Chemical Reversibility of Regenerative Reaction-Theoretical Analysis in Cyclic Voltammetry

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