Investigation on the interaction between anthracyclines and DNA in the presence of paclitaxel by resonance light scattering technique

Abstract

We have developed a method to investigate the interaction between DNA-targeted anthracyclines and DNA in the presence of the drug paclitaxel. It is based on resonance light scattering (RLS) and on the finding that anthracyclines when bound to DNA undergo a dramatic enhancement in their RLS intensities, while paclitaxel does not display such an effect. However, the RLS intensities of the anthracyclines-DNA associates are remarkably enhanced again on addition of paclitaxel. UV-visible spectra reveal interactions between paclitaxel and anthracyclines, but no reaction between paclitaxel and DNA. Consequently, paclitaxel, though not DNA-targeted, can improve the DNA-binding capabilities of anthracyclines. Binding constants between anthracyclines and DNA, and improved efficiency of paclitaxel on the DNA-binding capabilities of anthracyclines were calculated. The DNA binding constants of doxorubicin, epirubicin, and mitoxantrone, respectively, are 4.53 × 105 L mol−1, 6.05 × 105 L mol−1, and 9.47 × 105 L mol−1. The improved values in presence of paclitaxel are 78%, 47% and 19%. We also have investigated the effects of drug concentrations and the order of adding the drugs. Displacement studies (using methylene blue as a competitive agent) provided additional information on the mechanisms of the interaction between paclitaxel and anthracyclines.