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) has been reported in several systems. In the current work, the cellular effects generated by the DC treatment of the human leukemic K562 cell line and its vincristine-resistant derivative K562-Lucena 1 were analyzed by trypan blue staining and transmission electron microscopy. DC stimulation induced cell lysis, alterations in shape, membrane extraction or discontinuity, and intense vacuolization of some cells. In addition, treatment of K562 and K562-Lucena 1 cells caused a marked decrease in viability. Since multidrug resistance is a major factor contributing with failure of chemotherapy in many tumors, the expression and function of P-glycoprotein (P-gp) in K562-Lucena 1 cells were also studied. The expression of mdr1, the gene encoding P-gp, was analyzed by reverse transcription polymerase chain reaction, which showed that this gene was equally expressed in either treated or untreated cells. 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 cells, but affects their viability by mechanisms that would involve clear cellular effects, but also additional targets, whose relevance in dc treated tumoral cells is currently discussed.
Holandino
C
C
Departamento de Medicamentos-Faculdade de Farmácia, Instituto de Biofisica Carlos Chagas Filho, Rio de Janeiro, Brazil.
Veiga
V F
VF
Rodrigues
M L
ML
Morales
M M
MM
Capella
M A
MA
Alviano
C S
CS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division; D002470:Cell Survival / Q000502:physiology*; D018432:Drug Resistance, Multiple; D004558:Electric Stimulation / Q000379:methods; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal