Doxorubicin and genomic DNA, new insights in drug-nucleic acids interactions
| Authors | |
|---|---|
| Year of publication | 2009 |
| Type | Article in Periodical |
| Magazine / Source | International Journal of Molecular Medicine |
| MU Faculty or unit | |
| 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. |