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

Riccioni, Roberta; Dupuis, Maria Luisa; Bernabei, Manuela; Petrucci, Eleonora; Pasquini, Luca; Mariani, Gualtieri; Cianfriglia, Maurizio; Testa, Ugo

doi:10.1016/j.bcmd.2010.03.008

Cited by 138 publications

(99 citation statements)

References 26 publications

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“…A follow-up publication documented that salinomycin induces apoptosis in resistant cells, such as those expressing high levels of Bcl-2 and p-glycoprotein (Fuchs et al, 2009). Similar findings were also reported by Riccioni et al (2010). Multidrug resistance, mediated by the ABC transporter proteins, was overcome by salinomycin in leukemic stem-like cells, inducing the resilient cells into apoptosis (Fuchs et al, 2010).…”

Section: Compounds That Kill Cancer Stem-like Cellssupporting

confidence: 55%

Drugs that Kill Cancer Stem-like Cells

Zobalova¹,

Stantic²,

Stapelberg³

et al. 2011

Cancer Stem Cells Theories and Practice

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Section: Compounds That Kill Cancer Stem-like Cellssupporting

confidence: 55%

Drugs that Kill Cancer Stem-like Cells

Zobalova¹,

Stantic²,

Stapelberg³

et al. 2011

Cancer Stem Cells Theories and Practice

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“…It appears to reverse resistance mediated by ABC transporter family members 21 and may enhance cytotoxic drug efficacy through inhibiting the P-glycoprotein (ABCB1) member of this family. 22 The pertinence of such chemosensitizing mechanisms to salinomycin's action in single-drug use is presently unknown.…”

Section: Methodsmentioning

confidence: 99%

Detecting and targeting mesenchymal-like subpopulations within squamous cell carcinomas

et al. 2011

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“…NIG is a K + /H + ionophore derived from S. hygroscopicus that has been recently shown to overcome multidrug resistance of cancer cells 27 and to target CSCs. 15,[28][29][30] However, a recent study found that stem-like ovarian cancer cells expressing high levels of ABC drug transporters were largely resistant to ionophore antibiotics (IAs) such as salinomycin and NIG suggesting that IAs alone cannot eliminate certain CSLCs. 31,32 NIG also inhibits cellular processes associated with increased stemness such as metastasis and epithelial mesenchymal transition (EMT) in colorectal 16 and breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Nigericin decreases the viability of multidrug-resistant cancer cells and lung tumorspheres and potentiates the effects of cardiac glycosides

et al. 2017

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Multiple factors including tumor heterogeneity and intrinsic or acquired resistance have been associated with drug resistance in lung cancer. Increased stemness and the plasticity of cancer cells have been identified as important mechanisms of resistance; therefore, treatments targeting cancer cells independent of stemness phenotype would be much more effective in treating lung cancer. In this article, we have characterized the anticancer effects of the antibiotic Nigericin in cells displaying varying degrees of stemness and resistance to anticancer drugs, arising from (1) routine culture conditions, (2) prolonged periods of serum starvation. These cells are highly resistant to conventional anticancer drugs such as Paclitaxel, Hydroxyurea, Colchicine, Obatoclax, Wortmannin, and LY294002, and the multidrug-resistant phenotype of cells growing under prolonged periods of serum starvation is likely the result of extensive rewiring of signaling pathways, and (3) lung tumorspheres that are enriched for cancer stem-like cells. We found that Nigericin potently inhibited the viability of cells growing under routine culture conditions, prolonged periods of serum starvation, and lung tumorspheres. In addition, we found that Nigericin downregulated the expression of key proteins in the Wnt canonical signaling pathway such as LRP6, Wnt5a/b, and β-catenin, but promotes β-catenin translocation into the nucleus. The antitumor effects of Nigericin were potentiated by the Wnt activator HLY78 and by therapeutic levels of the US Food and Drug Administration-approved drug Digitoxin and its novel synthetic analog MonoD. We believe that Nigericin may be used in a co-therapy model in combination with other novel chemotherapeutic agents in order to achieve potent inhibition of cancers that display varying degrees of stemness, potentially leading to sustained anticancer effects.

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

Cited by 138 publications

References 26 publications

Drugs that Kill Cancer Stem-like Cells

Drugs that Kill Cancer Stem-like Cells

Detecting and targeting mesenchymal-like subpopulations within squamous cell carcinomas

Nigericin decreases the viability of multidrug-resistant cancer cells and lung tumorspheres and potentiates the effects of cardiac glycosides

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