The effect of chromatin compaction modification on the efficacy of anticancer medicaments

Abstract

Genomic DNA of eukaryotic cells is packaged in a nuclear complex called chromatin that serves as a regulatory platform by limiting nuclear machinery access to DNA. This work goal was to explore whether chromatin has a similar effect on drug-DNA binding. Previous results obtained in our group show that Ag3-AQCs reduce chromatin compaction and improve the efficacy of drugs like oxaliplatin, carboplatin, CDDP and DOX. In this work we explored whether this mechanism is specific, or if a reduction in chromatin compaction can improve DNA accessibility to drugs and, therefore, chemotherapeutic medicaments efficacy. Changing chromatin compaction increased CDDP and DOX binding to DNA in genetic and pharmacological models.