Publication details

Doxorubicin and genomic DNA, new insights in drug-nucleic acids interactions

Authors

MASAŘÍK Michal HÚSKA Dalibor ADAM Vojtěch BURDA V. Jaroslav ECKSCHLAGER Tomáš STIBOROVÁ Marie KIZEK René

Year of publication 2009
Type Article in Periodical
Magazine / Source International Journal of Molecular Medicine
MU Faculty or unit

Faculty of Medicine

Citation
Field Electrochemistry
Keywords Doxorubicin; DNA; electrochemistry; drug-DNA interaction
Description Anthracyclines including doxorubicin are commonly used in the treatment of a number of diverse malignant. There is compelling evidence that cellular DNA is the primary target for anthracyclines. In this study we aimed at investigation of intercalation of doxorubicin into DNA in vitro by using of square wave voltammetry coupled with adsorptive transfer stripping technique. Based on the decline of the signal of adenine and cytosine, we indicated binding of doxorubicin into dsDNA. The electrochemical method was further utilized for detection of doxorubicin-DNA adducts in neuroblastoma cells. Prior to electrochemical analysis dsDNA was carefully isolated from these cells to avoid modification of DNA bases. We observed significant (a=0.05) difference in DNA signals after intercalation of doxorubicin between resistant and sensitive cells. For more comprehensive understanding of the intercalation, computational experiments using design for testability approach with correction on dispersion interaction were performed. Several molecular structures were explored and clear preference for very stable stacked structures was observed.

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