title: The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor.
abstract: 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.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Riccioni
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Dupuis
authors.forename: Manuela
authors.initials: M
authors.lastname: Bernabei
authors.forename: Eleonora
authors.initials: E
authors.lastname: Petrucci
authors.forename: Luca
authors.initials: L
authors.lastname: Pasquini
authors.forename: Gualtieri
authors.initials: G
authors.lastname: Mariani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cianfriglia
authors.forename: Ugo
authors.initials: U
authors.lastname: Testa
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology*; D015854:Up-Regulation; D000095662:Polyether Polyketides
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides