The Anticancer Drug Daunomycin Directly Affects Gene Expression and DNA Structure

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6631
• Main Authors: Nishio, Takashi, Shimada, Yohji, Yoshikawa, Yuko, Kenmotsu, Takahiro, Schiessel, Helmut, Yoshikawa, Kenichi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2023; MDPI
• Subjects: Anthracycline; Anthracyclines; Antibiotics, Antineoplastic - pharmacology; anticancer drug; Atomic force microscopy; Cancer; Cell-free system; Communication; Daunomycin; Daunorubicin - pharmacology; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA damage; DNA structure; double-strand breaks (DSBs); Gene Expression; Genes; Genetic research; higher-order structure of DNA; Medical equipment and supplies industry; Medical test kit industry; Microscopy; Nucleic Acid Conformation; polyamine; Polyamines; Spermine; Spermine - pharmacology; United States; Japan; polyamine; anticancer drug; double-strand breaks (DSBs); cell-free in vitro luciferase assay; atomic force microscopy (AFM); daunomycin; higher-order structure of DNA; gene expression
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076631

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.