The ascidian natural product eusynstyelamide B is a novel topoisomerase II poison that induces DNA damage and growth arrest in prostate and breast cancer cells. Homo sapiens

As part of an anti-cancer natural product drug discovery program, we recently identified eusynstyelamide B (EB), which displayed cytotoxicity against MDA-MB-231 breast cancer cells. Here, we investigated the mechanism of action of EB in the prostate cancer cell line LNCaP after a treatment with 5 uM for 24 h. Transcriptome profiling followed by pathway analysis suggested that EB activated DNA damage pathways in LNCaP cells. Consistent with this, Chk2 phosphorylation was increased, p21Cip/Waf1 was up-regulated and Cdc2 expression was strongly reduced by EB. Importantly, EB caused DNA double-strand breaks, yet did not directly interact with DNA. Analysis of topoisomerase II-mediated decatenation discovered that EB is a novel topoisomerase II poison. Overall design: The dataset was derived from three independent biological repeats of each of the three treatment groups: untreated, DMSO-vehicle treated, eusynstyelamide B (EB) treated.