engleski

Modulation of membrane potential by Proprietary Potassium Ionophores in Breast Cancer Stem Cell Model

Cancer stem cells (CSCs) represent a subpopulation of cancer cells responsible for tumor formation, relapse and metastasis. Membrane depolarization might be important for the emergence and maintenance of CSCs, and moreover, highly metastatic cancer cells maintain high potassium concentrations. Potassium channels are involved in the promotion of tumorigenesis, but the data on their expression in CSCs are scarce. Breast CSC model established by Weinberg group enabled large screening of compounds for selectivity against CSCs. The most selective compound identified was salinomycin, a natural potassium ionophore. Based on the above mentioned studies and anticancer activity of crown-ethers that act as K+ ionophores, previously published by our group (1, 2), we hypothesized that these compounds could show activity towards CSCs by modulation of membrane potential. In the breast CSC model, cells with down- regulated Ecad expression (HMLEshEcad) are showing markers of CSC. Membrane potential after treatment with crown-ethers was estimated using the cationic dye DioC6(3). Highly cytotoxic compounds also modulated membrane potential. Although related by structure, one depolarized, while other hyperpolaryzed cells. Our observations will be further corroborated by electrophysiological and potassium concentration measurements, as well as with expression analysis of several representative potassium channels.

Breast cancer stem cells; Membrane potential; Potassium Ionophores

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