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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Salinomycin increases chemosensitivity to the effects of doxorubicin in soft tissue sarcomas

Authors: Sven-T Liffers, Daniel J Tilkorn, Ingo Stricker, Christoph Günter Junge, Sammy Al-Benna, Markus Vogt, Berlinda Verdoodt, Hans-U Steinau, Andrea Tannapfel, Iris Tischoff, Alireza Mirmohammadsadegh

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Chemotherapy for soft tissue sarcomas remains unsatisfactory due to their low chemosensitivity. Even the first line chemotherapeutic agent doxorubicin only yields a response rate of 18-29%. The antibiotic salinomycin, a potassium ionophore, has recently been shown to be a potent compound to deplete chemoresistant cells like cancer stem like cells (CSC) in adenocarcinomas. Here, we evaluated the effect of salinomycin on sarcoma cell lines, whereby salinomycin mono- and combination treatment with doxorubicin regimens were analyzed.

Methods

To evaluate the effect of salinomycin on fibrosarcoma, rhabdomyosarcoma and liposarcoma cell lines, cells were drug exposed in single and combined treatments, respectively. The effects of the corresponding treatments were monitored by cell viability assays, cell cycle analysis, caspase 3/7 and 9 activity assays. Further we analyzed NF-κB activity; p53, p21 and PUMA transcription levels, together with p53 expression and serine 15 phosphorylation.

Results

The combination of salinomycin with doxorubicin enhanced caspase activation and increased the sub-G1 fraction. The combined treatment yielded higher NF-κB activity, and p53, p21 and PUMA transcription, whereas the salinomycin monotreatment did not cause any significant changes.

Conclusions

Salinomycin increases the chemosensitivity of sarcoma cell lines - even at sub-lethal concentrations - to the cytostatic drug doxorubicin. These findings support a strategy to decrease the doxorubicin concentration in combination with salinomycin in order to reduce toxic side effects.
Appendix
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Metadata
Title
Salinomycin increases chemosensitivity to the effects of doxorubicin in soft tissue sarcomas
Authors
Sven-T Liffers
Daniel J Tilkorn
Ingo Stricker
Christoph Günter Junge
Sammy Al-Benna
Markus Vogt
Berlinda Verdoodt
Hans-U Steinau
Andrea Tannapfel
Iris Tischoff
Alireza Mirmohammadsadegh
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-490

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