Effect of salinomycin on EMT and stemness pathways in 5-FU-resistant breast cancer

Abstract

Cancer stem cells (CSCs) present in tumours are the primary cause of cancer recurrence and mediates resistance against therapeutic intervention. CSC properties like epithelial-to-mesenchymal transition (EMT) and cancer stemness lead to metastasis, quiescence and clonogenicity. Thus, there is a need for drug targeting CSCs; salinomycin is an efficient compound to achieve the same. Here, we report the effect of salinomycin on EMT and stemness pathway in chemoresistant breast cancer cells.Multiple treatments of breast cancer cells with 5-FU resulted in chemoresistant cells exhibiting a significant increase of cancer stemness and EMT markers like snail, zeb1, sox2. These cells had profound migratory and clonogenic features. A single dosage of salinomycin was sufficient to reduce the observed EMT and stemness markers associated with drug resistance. Further, the salinomycin treatment arrested the cell cycle at G2/M phase. Thus, our results demonstrated that salinomycin potentially eliminates breast CSCs.

Keywords

• Cancer relapse
• Cancer stem cells
• Drug resistance
• EMT
• Stemness
• Salinomycin