Journal
STEM CELLS TRANSLATIONAL MEDICINE
Volume 4, Issue 9, Pages 1028-1032Publisher
ALPHAMED PRESS
DOI: 10.5966/sctm.2015-0054
Keywords
Ionophore antibiotic; Salinomycin; Nigericin; Cancer stem cell; Drug transporter
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Funding
- Oncotyrol
- Competence Center Oncotyrol
- Oesterreichische Krebshilfe Tirol
- Deutsche Forschungsgemeinschaft
- Austrian Society of Hemato-Oncology
- Forschungsfonds of the Austrian National Bank
- Tiroler Landeskrankenanstalten
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Ionophore antibiotics were reported to selectively kill cancer stem cells and to overcome multidrug resistance, but mechanistic studies of the significance of drug transporters for treatment with these compounds are lacking. We applied chemosensitivity testing of well-characterized human cancer cell lines to elaborate on whether drug transporters are involved in protection from the cytotoxic effects of the ionophore antibiotics salinomycin and nigericin. Our experiments demonstrated that ionophore antibiotics were ineffective against both stem-like ovarian cancer side population cells (expressing either ABCB1 or ABCG2) and K562/Dox-H1 cells, which constitute a genetically defined model system for ABCB1 expression. Considering that cancer stem cells often express high levels of drug transporters, we deduced from our results that ionophore antibiotics are less suited to cancer stem cell-targeted treatment than previously thought.
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