Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species

  • \(\textit {Background:}\) Salinomycin is a polyether ionophore antibiotic that has recently been shown to induce cell death in human cancer cells displaying multiple mechanisms of drug resistance. The underlying mechanisms leading to cell death after salinomycin treatment have not been well characterized. We therefore investigated the role of salinomycin in caspase dependent and independent cell death in colon cancer (SW480, SW620, RKO) and breast cancer cell lines (MCF-7, T47D, MDA-MB-453). \(\textit {Methodology/Principal Findings:}\) We detected features of apoptosis in all cell lines tested, but the executor caspases 3 and 7 were only strongly activated in RKO and MDA-MB-453 cells. MCF-7 and SW620 cells instead presented features of autophagy such as cytoplasmic vacuolization and LC3 processing. Caspase proficient cell lines activated autophagy at lower salinomycin concentrations and before the onset of caspase activation. Salinomycin also led to the formation of reactive oxygen species (ROS) eliciting JNK activation and induction of the transcription factor \(\it JUN\). Salinomycin mediated cell death could be partially inhibited by the free radical scavenger N-acetyl-cysteine, implicating ROS formation in the mechanism of salinomycin toxicity. \(\textit {Conclusions:}\) Our data indicate that, in addition to its previously reported induction of caspase dependent apoptosis, the initiation of autophagy is an important and early effect of salinomycin in tumor cells.

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Metadaten
Author:Berlinda VerdoodtGND, Markus VogtORCiDGND, Inge SchmitzGND, Sven-Thorsten LiffersGND, Andrea TannapfelORCiDGND, Alireza MirmohammadsadeghGND
URN:urn:nbn:de:hbz:294-72831
DOI:https://doi.org/10.1371/journal.pone.0044132
Parent Title (English):PLoS ONE
Publisher:Public Library of Science
Place of publication:San Francisco
Document Type:Article
Language:English
Date of Publication (online):2020/07/03
Date of first Publication:2012/09/19
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Volume:7
Issue:9, Artikel e44132
First Page:e44132-1
Last Page:e44132-13
Institutes/Facilities:Institut für Pathologie
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International