The Anticancer Drug Daunomycin Directly Affects Gene Expression and DNA Structure

Daunomycin (DM), an anthracycline antibiotic, is frequently used to treat various cancers, but the direct effects of DM on gene expression and DNA structure are unclear. We used an in vitro cell-free system, optimized with spermine (SP), to study the effect of DM on gene expression. A bimodal effect of DM on gene expression, weak promotion followed by inhibition, was observed with increasing concentration of DM. We also performed atomic force microscopy observation to measure how DM affects the higher-order structure of DNA induced with SP. DM destroyed SP-induced flower-like conformations of DNA by generating double-strand breaks, and this destructive conformational change of DNA corresponded to the inhibitory effect on gene expression. Interestingly, the weakly enhanced cell-free gene expression occurred as DNA conformations were elongated or relaxed at lower DM concentrations. We expect these newly unveiled DM effects on gene expression and the higher-order structure of DNA will contribute further to the development and refinement of useful anticancer therapy chemicals.

Automated summary

In this study, we used an in vitro cell-free system with spermine to investigate the effect of daunomycin (DM) on gene expression. We found that DM exhibits a bimodal effect on gene expression, promoting at lower concentrations and inhibiting at higher concentrations. Through atomic force microscopy observation, we observed that DM destroys flower-like conformations of DNA induced by spermine, resulting in double-strand breaks. These newly revealed effects of DM on gene expression and DNA structure will contribute to the development and refinement of anticancer therapy chemicals.