Salinomycin: A new paradigm in cancer therapy

Dewangan, Jayant; Srivastava, Sonal; Rath, Srikanta Kumar

doi:10.1177/1010428317695035

Cited by 109 publications

(69 citation statements)

References 99 publications

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“…We further determined the effect of salinomycin on ethanol‐induced EMT. Salinomycina is drug targeted to kill CSCs and could inhibit Wnt/ β ‐catenin signaling pathway . We showed that salinomycin treatment (2.5 μM and 24 h) effectively inhibited Wnt/ β ‐catenin signaling (Supplementary material: Figure S4A‐F).…”

Section: Resultsmentioning

confidence: 95%

Epithelial to mesenchymal transition is involved in ethanol promoted hepatocellular carcinoma cells metastasis and stemness

Chen

Wang

et al. 2018

Molecular Carcinogenesis

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Hepatocellular Carcinoma (HCC) is a malignant tumor with high rate of relapse and metastasis. Ethanol is a well‐known risk factor for HCC; it promotes the progression and aggressiveness of HCC. However, the underlying mechanism remains unclear. In clinic studies, we showed that alcohol consumption is positively correlated with TNM stage and vessel invasion; HCC patients with chronic drinking history had faster progression rate and poorer prognosis compared to non‐drinkers. In experimental models, ethanol exposure enhanced the metastasis, and invasion of HCC cells. Ethanol exposure increased cancer stem cells (CSC) population and enhanced stemness of HCC cells in vitro and in vivo. Mechanically, we found that ethanol exposure induced epithelial to mesenchymal transition (EMT) through activating Wnt/β‐catenin signaling pathway in HCC cells. We further demonstrated that β‐catenin siRNA or salinomycin (an inhibitor of Wnt/β‐catenin pathway) partially rescued ethanol‐induced EMT. In conclusion, this study suggested that ethanol exposure promotes the metastasis and stemness of HCC cells by inducing EMT.

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Section: Resultsmentioning

confidence: 95%

Epithelial to mesenchymal transition is involved in ethanol promoted hepatocellular carcinoma cells metastasis and stemness

Chen

Wang

et al. 2018

Molecular Carcinogenesis

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“…Our group and other groups have demonstrated that salinomycin could inhibit proximal Wnt signalling by blocking LRP6 phosphorylation and inducing its degradation (Dewangan et al, ; D. Lu et al, ; W. Lu & Li, ). In our previous studies, micromolar concentrations of salinomycin were needed to block Wnt signalling induced by downstream activators, such as β‐catenin, suggesting additional mechanisms must be involved in the inhibitory effect of salinomycin on Wnt signalling (D. Lu et al, ).…”

Section: Discussionmentioning

confidence: 83%

“…However, the molecular mechanisms by which salinomycin targets CSCs is poorly understood. Several potential mechanisms have been suggested (Dewangan, Srivastava, & Rath, ), including suppression of the ATP‐binding cassette (ABC) transporter (Fuchs, Daniel, Sadeghi, Opelz, & Naujokat, ; Kim et al, ) and blocking of pathways implicated in cancer such as Akt (Kuo et al, ), Wnt (D. Lu et al, ; D. Lu & Carson, ), Hedgehog (Y. Lu et al, ), and Notch (Zhou et al, ).…”

Section: Introductionmentioning

confidence: 99%

Salinomycin exerts anti‐colorectal cancer activity by targeting the β‐catenin/T‐cell factor complex

Wang

Zhou

Xiong

et al. 2019

British J Pharmacology

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Background and Purpose Salinomycin is a well‐known inhibitor of human cancer stem cells ( CSCs ). However, the molecular mechanism(s) by which salinomycin targets colorectal CSCs is poorly understood. Here, we have investigated underlying antitumour mechanisms of salinomycin in colorectal cancer cells and three tumour models. Experimental Approach The inhibitory effect of salinomycin on the Wnt/β‐catenin pathway was analysed with the SuperTopFlash reporter system. The mRNA expression of Wnt target genes was evaluated with real‐time PCR. Effects of salinomycin on β‐catenin/TCF4E interaction were examined using co‐immunoprecipitation and an in vitro GST pull‐down assay. Cell proliferation was determined by BrdU incorporation and soft agar colony formation assay. The stemness of the cells was assessed by sphere formation assay. Antitumour effects of salinomycin on colorectal cancers was evaluated with colorectal CSC xenografts, APC min/+ transgenic mice, and patient‐derived colorectal tumour xenografts. Key Results Salinomycin blocked β‐catenin/TCF4E complex formation in colorectal cancer cells and in an in vitro GST pull‐down assay, thus decreasing expression of Wnt target genes. Salinomycin also suppressed the transcriptional activity mediated by β‐catenin/LEF1 or β‐catenin/TCF4E complex and exhibited an inhibitory effect on the sphere formation, proliferation, and anchorage‐independent growth of colorectal cancer cells. In colorectal tumour xenografts and APC min/+ transgenic mice, administration of salinomycin significantly reduced tumour growth and the expression of CSC‐related Wnt target genes including LGR5. Conclusions and Implications Our study suggested that salinomycin could suppress the growth of colorectal cancer by disrupting the β‐catenin/TCF complex and thus may be a promising agent for colorectal cancer treatment.

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“…Since Twist1 expression is restricted to tumor cells, it represents a very interesting target. Efforts to develop specific drugs or inactivation system remain to be done, even some are promising [41].…”

Section: Resultsmentioning

confidence: 99%

“…There are different drugs currently in development targeting the cancer stem cells associated with Twist1 deregulation. Some show promising results from preclinical trials like Salinomycin able to effectively eliminate CSCs and to induce partial clinical regression of heavily pretreated and therapy-resistant cancers [40,41].…”

Section: Twist1 Targeted Therapymentioning

confidence: 99%

Considerations for the Development of Innovative Therapies Against Aggressive Neuroblastoma: Immunotherapy and Twist1 Targeting

Shekarian¹,

Valsesia‐Wittmann²

2017

Neuroblastoma - Current State and Recent Updates

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Neuroblastoma (NB) is one of the major challenges of pediatric oncology with a 5-year survival rate of less than 40% despite intense therapy. The aggressiveness of the disease has been recently correlated to the degree of myeloid cells infiltrating the tumor. Together with the tumor cells and immunosuppressive cytokines (e.g., IL-10 and TGF-β), these cells hamper the generation of an efficient antitumor immune response and, therefore, favor tumor growth and metastasis. Novel therapeutic approaches are designed to target immune cells instead of cancer cells. To improve their efficacy, recent cancer immunotherapy strategies have focused on the depletion, blockade, or reprogramming of these tolerogenic immune effectors. Therefore, the principal clinical challenge is currently to identify therapeutic strategies which could overcome the primary and secondary resistances to these cancer immunotherapies. In this review, we discuss the dialogue of immune microenvironment of neuroblastoma and the immunotherapeutic strategies to cure neuroblastoma.

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Salinomycin: A new paradigm in cancer therapy

Cited by 109 publications

References 99 publications

Epithelial to mesenchymal transition is involved in ethanol promoted hepatocellular carcinoma cells metastasis and stemness

Epithelial to mesenchymal transition is involved in ethanol promoted hepatocellular carcinoma cells metastasis and stemness

Salinomycin exerts anti‐colorectal cancer activity by targeting the β‐catenin/T‐cell factor complex

Considerations for the Development of Innovative Therapies Against Aggressive Neuroblastoma: Immunotherapy and Twist1 Targeting

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