Toxicity of salinomycin in combination with cisplatin in MDR-1-positive HNSCC cell lines

Introduction The polyether antibiotic salinomycin has been identified as a potent growth inhibitor of epithelial cancer stem cells. Since then, numerous studies about its effects on different cancer cells have been published. In particular, salinomycin has been shown to inhibit the ABC transporter P-glycoprotein/MDR-1, which induces a neutralization of this resistance mechanism. Thus, the aim of this study was to evaluate the toxicity of salinomycin in combination with cisplatin in MDR-1 positive and negative head and neck squamous cell carcinoma (HNSCC) cell lines.

Material and methods HNSCC cell line PJ-41 and its MDR-1 positive clone PJ-41-ASM were used. After incubation of the cells with salinomycin (0,1 to 175µM), cisplatin (1 to 20µM) and a combination of both (concentration of salinimomycin: 10µM + concentrations of cisplatin: 5, 10 and 20µM) for 24 h, cytotoxic effects were investigated using the MTT assay and the Annexin V-propidium iodide test.

Results The MTT assay revealed a significant reduction of cell viability at salinomycin-concentrations above 10µM and cisplatin-concentrations above 20µM for both PJ-41 und PJ-41-ASM. For the combination of the two substances this effect was already shown at a cisplatin-concentration of 5µM. These results were confirmed by the Annexin V-propidium iodide test.

Conclusion In the present study, a synergistic effect of salinomycin and cisplatin in cytostatic-resistant and non-resistant HNSCC cell lines, independent from the MDR-1 expression, was demonstrated. Further investigation to evaluate toxicity of salinomycin combined with other chemotherapeutics is now in preparation.

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Conflict of interest

Der Erstautor gibt keinen Interessenskonflikt an.

Publication History

Article published online:
13 May 2021