1. Department of Chemistry, Shantou University, Shantou, 515063, China 2. Guangdong Pharmaceutical University, Guangzhou, 510006, China 3. Department of Radiology, Peking University Shenzhen Hospital, Shenzhen, 518036, China
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.
Figure
A novel resonance light scattering (RLS) method for the investigation on the interaction between anthracyclines and DNA in the presence of paclitaxel has been developed based on the enhanced RLS intensities.