Methylxanthines (caffeine, pentoxifylline and theophylline) decrease the mutagenic effect of daunomycin, doxorubicin and mitoxantrone

Previously performed experiments showed that methylxanthines, especially caffeine, may protect cells against cytostatic or cytotoxic effects of several aromatic compounds. One of the proposed mechanisms of this protection is based on stacking interactions between π electron systems of polycyclic aromatic molecules. In this work, we demonstrate that caffeine and other methylxanthines - pentoxifylline and theophylline - significantly decrease mutagenicity of the anticancer aromatic drugs daunomycin, doxorubicin and mitoxantrone. The spectrophotometric titration of these aromatic compounds by methylxanthines indicated formation of mixed aggregates. The concentrations of free active forms of the drugs decreased when the concentrations of methylxanthines increased in the mixture. Therefore, likely methylxanthines may play a role of scavengers of the free active forms of daunomycin, doxorubicin and mitoxantrone