Toxicity of Salinomycin 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. Thus, the aim of this study was to evaluate the toxicity of salinomycin in MDR-1 positive and negative head and neck squamous cell carcinoma (HNSCC) cell lines.

Material and methods:

HNSCC cell lines HLaC 79 and PJ-41 were used. Initially, the paclitaxel-resistant clones HLaC79 C1 and PJ-41- ASM were generated. RT-qPCR was performed to evaluate the expression levels of MDR-1. Cells were treated with salinomycin in concentrations ranging from 0,1 to 175µM. After 24h of incubation cytotoxic effects were investigated by MTT assay and Annexin V-propidium iodide test.

Results:

HLaC 79 and PJ-41 were identified as MDR-1 negative, while HLaC79 C1 and PJ-41-ASM showed high MDR-1 gene expression. The MTT assay revealed a significant reduction of cell viability at concentrations above 1µM in HLaC79 and HLaC79 C1. Furthermore, cytoxicity was shown for PJ-41 and PJ-ASM at concentrations above 10µM. Our results could be confirmed by the Annexin V-propidium iodide test.

Conclusions:

In the present study we could demonstrate that salinomycin is a potent inhibitor of cytostatic resistant and non-resistant HNSCC cell lines, independent from the MDR-1 expression. Prior to a possible clinical application, detailed investigations regarding its mechanisms of action and toxicity in malignant and non-malignant cells are necessary. In addition, synergistic effects of salinomycin and different chemotherapeutics should be evaluated.

Publication History

Publication Date:
23 April 2019 (online)