Inhibition of protein synthesis and JNK activation are not required for cell death induced by anisomycin and anisomycin analogues

David Monaghan, Enda O'Connell, Faye L. Cruickshank, Barry O'Sullivan, Francis J. Giles, Alison N. Hulme, Howard O. Fearnhead*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)761-767
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume443
Issue number2
DOIs
StatePublished - Jan 10 2014

Keywords

  • Apoptosis
  • Breast cancer
  • Drug-resistance
  • Ribotoxic stress

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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