Institution: | 1. Pharmacology and Therapeutics, National Centre for Biomedical Engineering Research, National University of Ireland Galway, Galway, Ireland;2. Screening Laboratory, National Centre for Biomedical Engineering Research, National University of Ireland Galway, Galway, Ireland;3. School of Chemistry, University of Edinburgh, UK;4. HRB Clinical Research Facility, Galway, Ireland |
Abstract: | Anisomycin was identified in a screen of clinical compounds as a drug that kills breast cancer cells (MDA16 cells, derived from the triple negative breast cancer cell line, MDA-MB-468) that express high levels of an efflux pump, ABCB1. We show the MDA16 cells died by a caspase-independent mechanism, while MDA-MB-468 cells died by apoptosis. There was no correlation between cell death and either protein synthesis or JNK activation, which had previously been implicated in anisomycin-induced cell death. In addition, anisomycin analogues that did not inhibit protein synthesis or activate JNK retained the ability to induce cell death. These data suggest that either a ribosome-ANS complex is a death signal in the absence of JNK activation or ANS kills cells by binding to an as yet unidentified target. |