The Anticancer Drug Daunomycin Directly Affects Gene Expression and DNA Structure

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Article number6631
Number of pages11
JournalInternational Journal of Molecular Sciences
Volume24
Issue number7
Publication statusPublished - Apr 2023
Peer-reviewedYes

External IDs

Scopus 85152319235
ORCID /0000-0001-8761-1776/work/132582628

Keywords

Sustainable Development Goals