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Biochem Biophys Res Commun. 2014 Jan 10;443(2):761-7. doi: 10.1016/j.bbrc.2013.12.041. Epub 2013 Dec 12.

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

Author information

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.
5
Pharmacology and Therapeutics, National Centre for Biomedical Engineering Research, National University of Ireland Galway, Galway, Ireland. Electronic address: howard.fearnhead@nuigalway.ie.

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.

KEYWORDS:

(2R,3R)-3-acetoxy-1-benzyl-2-(4-methoxybenzyl)pyrrolidine; (2R,3R,4S)-3-acetoxy-1-benzyl-2-(4-methoxybenzyl)-4-methylpyrrolidine; (2R,3S,4S)-1-benzyl-4-benzyloxy-3-hydroxy-2-(4-methoxybenzyl)pyrrolidine; (2R,3S,4S)-3-acetoxy-1-benzyl-4-benzyloxy-2-(4-methoxybenzyl)pyrrolidine; ANS; Apoptosis; Breast cancer; CHX; Compound 17; Compound 25; Compound 26; Compound 27; DMEM; DMSO; DTT; Drug-resistance; Dulbecco’s modified Eagle’s medium; FBS; HBSS; Hanks’ balanced salt solution; JNK; Jun kinase; PBS; PVDF; Ribotoxic stress; TBS; TNBC; anisomycin; cycloheximide; dimethyl sulfoxide; dithiolthreitol; fetal bovine serum; phosphate buffered saline; polyvinylidene difluoride; triple negative breast cancer; tris buffered saline

PMID:
24333448
DOI:
10.1016/j.bbrc.2013.12.041
[Indexed for MEDLINE]

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