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. 2022 Apr 15;12:6294. doi: 10.1038/s41598-022-10293-x

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© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Gene expression profiling shows two major cellular targets of Mitoxantrone. (A) A volcano plot showing genes upregulated or downregulated by Mitoxantrone in HEK293T cells. (B) A list of significant pathways upregulated by Mitoxantrone. (C) Genes encoding nucleosome proteins are highly upregulated by Mitoxantrone. Shown is a gene interaction network highlighting nucleosome assembly-related genes induced by Mitoxantrone. Colors indicate fold change. (D) A crystal structure shows the binding of Mitoxantrone to a DNA-topoisomerase complex. Arrows indicate the two Mitoxantrone molecules each associated with a topoisomerase monomer. (E,F) LigPlot views of the molecular interactions between Mitoxantrone and the DNA-topoisomerase complex.