Direct current decreases cell viability but not P-glycoprotein expression and function in human multidrug resistant leukemic cells

Inhibition of tumor growth induced by treatment with direct current (DC) ha s been reported in several systems. In the current work, the cellular effec ts generated by the DC treatment of the human leukemic K562 cell line and i ts vincristine-resistant derivative K562-Lucena I were analyzed by trypan b lue staining and transmission electron microscopy. DC stimulation induced c ell lysis, alterations in shape, membrane extraction or discontinuity, and intense vacuolization of some cells. In addition, treatment of K562 and K56 2-Lucena I cells caused a marked decrease in viability. Since multidrug res istance is a major factor contributing with failure of chemotherapy in many tumors, the expression and function of P-glycoprotein (P-gp) in K562-Lucen a 1 cells were also studied. The expression of mdr1, the gene encoding P-gp , was analyzed by reverse transcription polymerase chain reaction, which sh owed that this gene was equally expressed in either treated or untreated ce lls. These results were confirmed by flow cytometry with a monoclonal anti P-gp antibody and the Rhodamine 123 extrusion method, which revealed that P -gp surface expression and function were unaltered after DC treatment. Our results suggest that DC treatment does not affect P-gp in human leukemic ce lls, but affects their viability by mechanisms that would involve clear cel lular effects, but also additional targets, whose relevance in dc treated t umoral cells is currently discussed. (C) 2001 Wiley-Liss, Inc.