The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor

Salinomycin, a polyether antibiotic acting as a highly selective potassium ionophore and widely used as an anticoccidial drug, was recently shown to act as a specific inhibitor of cancer stem cells. In the present study we report that salinomycin acts as a potent inhibitor of multidrug resistance gp...

Full description

Saved in:
Bibliographic Details
Published in:Blood cells, molecules, & diseases molecules, & diseases, 2010-06, Vol.45 (1), p.86-92
Main Authors: Riccioni, Roberta, Dupuis, Maria Luisa, Bernabei, Manuela, Petrucci, Eleonora, Pasquini, Luca, Mariani, Gualtieri, Cianfriglia, Maurizio, Testa, Ugo
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Apoptosis
Apoptosis - drug effects
ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Cancer stem cells
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
Chemoresistance
Drug Resistance, Neoplasm - drug effects
Drugs
Humans
Neoplasms - drug therapy
Neoplastic Stem Cells - drug effects
Pyrans - pharmacology
Up-Regulation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Salinomycin, a polyether antibiotic acting as a highly selective potassium ionophore and widely used as an anticoccidial drug, was recently shown to act as a specific inhibitor of cancer stem cells. In the present study we report that salinomycin acts as a potent inhibitor of multidrug resistance gp170, as evidenced through drug efflux assays in MDR cancer cell lines overexpressing P-gp (CEM-VBL 10 and CEM-VBL 100; A2780/ADR). Conformational P-gp assay provided evidence that the inhibitory effect of salinomycin on P-gp function could be mediated by the induction of a conformational change of the ATP transporter. Treatment of the MDR cell lines with salinomycin restored a normal drug sensitivity of these cells. The observation that salinomycin is a MDR-1 inhibitor may have important implications for the understanding of the mechanisms through which this drug impairs the viability of cancer stem cells. Interestingly, nigericin and abamectin, two additional drugs identified as cancer stem cells inhibitors, also act as potent gp170 inhibitors.
ISSN:1079-9796
1096-0961
DOI:10.1016/j.bcmd.2010.03.008