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

BMC Cancer
Sven-T LiffersAlireza Mirmohammadsadegh

Abstract

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. 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. 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 sig...Continue Reading

References

Jul 1, 1994·CA: a Cancer Journal for Clinicians·C P Karakousis, R P Perez
Nov 27, 1999·The Journal of Biological Chemistry·X H PeiN Hara
Apr 29, 2000·Nature·K M RyanK H Vousden
Jan 23, 2004·Nature Reviews. Cancer·Ricardo PardalSean J Morrison
May 2, 2006·Cancer Letters·Hellinida ThomadakiAndreas Scorilas
Dec 5, 2006·Critical Reviews in Oncology/hematology·Bernd KasperAhmad Awada
Dec 8, 2006·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C E HumberJ A Green
May 16, 2009·Cell Death and Differentiation·P WangL Zhang
Aug 4, 2009·Archives of Biochemistry and Biophysics·Yahong ZhangTakashi Ikejima
Oct 20, 2009·Biochemical and Biophysical Research Communications·Dominik FuchsCord Naujokat
Mar 31, 2010·Biochemical and Biophysical Research Communications·Dominik FuchsCord Naujokat
Sep 8, 2010·Nature Cell Biology·Dongping LiuYang Xu

Citations

Sep 5, 2015·Bioorganic & Medicinal Chemistry Letters·Adam HuczyńskiJoanna Wietrzyk
Apr 11, 2014·Basic & Clinical Pharmacology & Toxicology·Rosi BissingerFlorian Lang
Jul 15, 2015·Bioorganic & Medicinal Chemistry Letters·Michał AntoszczakAdam Huczyński
Jul 16, 2014·Case Reports in Surgery·Emanuele GrassoMichele Simone
Feb 6, 2015·Acta Biochimica Et Biophysica Sinica·Bin XuJian Xu
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jayant DewanganSrikanta Kumar Rath
Feb 23, 2018·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Francesca PerutNicola Baldini
Aug 3, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeanne GalaineOlivier Adotévi
Jan 6, 2019·European Journal of Medicinal Chemistry·Michał Antoszczak

Methods Mentioned

BETA
xenograft
transfection
PCR
Assay
flow cytometry
caspase assay

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