E-GEOD-33624 - Distinct effects of topoisomerase II inhibitors on tumor cell lines (part 1)
Released on 4 June 2013, last updated on 2 June 2014
One major class of anti-cancer drugs targets topoisomerase II to induce DNA double-strand breaks and cell death of fast growing cells. Here, we compare three members of this class - the antracyclines doxorubicin and aclarubicin, and a chemically unrelated compound, etoposide. Aclarubicin does not induce DNA breaks. We define a new activity for the antracyclines: unsupported histone eviction from ´open´ or loosely packed chromosomal areas reflecting exon and promoter regions. As a result, the epigenome and the transcriptome are strongly affected. Tissue culture cells were treated with doxorubicin, aclarubicin or etoposide for 2 hours. Then drugs were removed by extensive washing. cells were further cultured for indicated days before total RNA were extracted and compared to un-treated control.
transcription profiling by array
Arno Velds, Baoxu Pang, Jacques Neefjes, Ron Kerkhoven
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. Pang B, Qiao X, Janssen L, Velds A, Groothuis T, Kerkhoven R, Nieuwland M, Ovaa H, Rottenberg S, van Tellingen O, Janssen J, Huijgens P, Zwart W, Neefjes J. , Europe PMC 23715267