Related Experiment Video
Updated: Oct 4, 2026
Modeling Chemotherapy Resistant Leukemia In Vitro
Published on: February 9, 2016
Direct current decreases cell viability but not P-glycoprotein expression and function in human multidrug resistant
C Holandino1, V F Veiga, M L Rodrigues
1Departamento de Medicamentos-Faculdade de Farmácia, Instituto de Biofisica Carlos Chagas Filho, Rio de Janeiro, Brazil.
Abstract:
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.
Insights
Direct current (DC) treatment effectively reduces human leukemic cell viability through direct cellular damage. This cancer therapy approach does not impact P-glycoprotein (P-gp) function, a key factor in multidrug resistance.
Area of Science:
- Oncology
- Cell Biology
- Biophysics
Background:
- Direct current (DC) therapy shows promise for inhibiting tumor growth.
- Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy, often mediated by P-glycoprotein (P-gp).
Purpose of the Study:
- To investigate the cellular effects of DC treatment on human leukemic K562 cells and their vincristine-resistant counterpart, K562-Lucena 1.
- To determine if DC treatment affects P-glycoprotein (P-gp) expression and function in these cells.
Main Methods:
- Cell viability was assessed using trypan blue staining.
- Cellular morphology and ultrastructure were examined via transmission electron microscopy.
- P-glycoprotein (P-gp) expression and function were analyzed using reverse transcription polymerase chain reaction, flow cytometry, and Rhodamine 123 extrusion assays.
Main Results:
- DC treatment induced significant cellular effects, including lysis, shape alteration, membrane discontinuity, and vacuolization, leading to decreased cell viability.
- The expression of the mdr1 gene, which encodes P-gp, remained unchanged after DC treatment.
- P-gp surface expression and efflux function were unaltered by DC treatment in K562-Lucena 1 cells.
Conclusions:
- DC treatment effectively reduces leukemic cell viability through direct cellular damage, independent of P-gp modulation.
- The findings suggest that DC therapy targets leukemic cells via mechanisms distinct from P-gp activity, offering a potential strategy against MDR cancers.
Related Concept Videos
02:56Treatment Resistant Cancers
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:23Abnormal Proliferation