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Exploring the relationship between cytoplasmic ion content variation and multidrug resistance in cancer cells via ion-release based impedance spectroscopy

Demircan Yalçın, Yağmur
Sukas, Sertan
Töral, Taylan Berkin
Gündüz, Ufuk
Külah, Haluk
This study aimed to measure and compare the cytoplasmic ion concentrations of the parental cells and their drug resistant progenies. High-level laboratory and clinically-relevant multidrug resistance (MDR) cell line models were developed and investigated for K562 and CCRF-CEM cells, respectively. Measurements were achieved using a modified version of ion release-based impedance spectroscopy (IRbIS), where the average total ion concentration per cell was determined by measuring the variations in solution conductance after the lysis of a population with a known initial cell count. Results showed that the average of cytoplasmic ion concentration for K562/imaR cells was almost 1.8 times higher than that of K562/wt cells with a standard error of mean (SEM) lower than 7%, having a significant difference at p = 0.05 level. CCRF-CEM/doxR cells had almost a 1.2-fold increase in the ion concentration compared with CCRF-CEM/wt cells with an SEM smaller than 11%. Unlike K562 cells, this was not a significant variation at p = 0.05 level. Having insignificant SEMs proved the validity of this modified implementation of IRbIS measurements. We showed that our new approach enables to identify variations in cytoplasmic ion concentration per cell and to understand the mechanisms driving the toxicity and the development of drug resistance to chemotherapeutic agents.