Anisomycin analogues induce cell
death in multi-drug-resistant cancer cells in the absence of JNK activation and
protein synthesis inhibition
David Monaghan1, Enda O’Connell2, Faye L. Cruikshank3,
Francis J. Giles4,5, Francis J. Sullivan4,5, Alison N.
Hulme3, Howard O. Fearnhead1
1Pharmacology and Therapeutics, 2Screening Laboratory,
National Centre for Biomedical Engineering Research, National University of
Ireland Galway, Galway, Ireland, 3School of Chemistry, University of
Edinburgh, UK, 4Prostate Cancer Institute, National University of
Ireland, Galway, 5HRB Clinical Research Facility, Galway.
identified in a screen of clinical compounds as a drug that kills a multi-drug
resistant breast cancer cell line as well as other triple-negative breast and
prostate cancer lines. We show for the first time that anisomycin analogues
that do not inhibit protein synthesis or activate JNK retain the ability to
induce cell death. Our findings significantly strengthen the case for
re-purposing anisomycin and the development of anisomycin analogues for the
treatment of drug-resistant cancers.