Abstract
The recently described method of cell electroporation by flow of cell suspension through localized direct current electric fields (dcEFs) was applied to identify non-toxic substances that could sensitize cells to external electric fields. We found that local cationic anesthetics such as procaine, lidocaine and tetracaine greatly facilitated the electroporation of AT2 rat prostate carcinoma cells and human skin fibroblasts (HSF). This manifested as a 50% reduction in the strength of the electric field required to induce cell death by irreversible electroporation or to introduce fluorescent dyes such as calcein, carboxyfluorescein or Lucifer yellow into the cells. A similar decrease in the electric field thresholds for irreversible and reversible cell electroporation was observed when the cells were exposed to the electric field in the presence of the non-toxic cationic dyes 9-aminoacridine (9-AAA) or toluidine blue. Identifying non-toxic, reversibly acting cell sensitizers may facilitate cancer tissue ablation and help introduce therapeutic or diagnostic substances into the cells and tissues.
Highlights
In the past few decades, reversible electroporation (RE) has been broadly used to introduce substances that normally do not penetrate the cell membrane, such as dyes, drugs, proteins and nucleic acids, into cells [1,2,3]
Both lidocaine and tetracaine significantly decreased the threshold values of direct current electric field (dcEF) required for irreversible electroporation (IRE), when compared with the values of dcEFs required for cell killing by IRE in the control experiments in the absence of the tested cationic anesthetics
We tested whether other non-toxic cationic substances, such as toluidine blue (15 uM) [13] or 9-AAA (30 μM) [22, 23], would influence the threshold values of dcEFs required for cell killing by IRE
Summary
In the past few decades, reversible electroporation (RE) has been broadly used to introduce substances that normally do not penetrate the cell membrane, such as dyes, drugs, proteins and nucleic acids, into cells [1,2,3]. We used the recently described the method of cell electroporation using a flow of cell suspension through a localized electric field [10] to examine the effects of substances known to modify cell membrane properties. This method allows the numbers of reversibly and irreversibly electroporated cells to be determined as a function of dcEF applied to the cells for a given period of time (time duration). The experiments were carried out on a rat prostate cell line and human skin fibroblasts (HSF) using anesthetics at lower concentrations than commonly used in surgical anesthesia
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