Combined effects of doxorubicin and STI571 on growth, differentiation and apoptosis of CML cell line K562

• Authors: Justyna Jakubowska , Marta Stasiak , Agata Szulawska , Andrzej Bednarek , Malgorzata Czyz
• Languages of publication: EN

Abstracts

EN

STI571 (imatinib mesylate; Gleevec®) is an inhibitor that targets the tyrosine kinase activity of Bcr-Abl present in chronic myelogenous leukemia (CML) cells. Some preclinical studies have demonstrated that the combination of STI571 with chemotherapeutic drugs results in enhanced toxicity in Bcr-Abl-positive leukemias. We investigated the potential benefit of using STI571 to down-regulate Bcr-Abl activity for the enhancement of doxorubicin anti-proliferative action in K562 cell line derived from blast crisis of CML. At low concentrations of both drugs (40 nM doxorubicin combined with STI571 in the range of 100-150 nM), the antiproliferative effects were mainly due to cellular differentiation as assessed by benzidine staining for hemoglobin synthesis level and real-time PCR for γ-globin expression. Higher concentrations of STI571 used in combinations with doxorubicin caused mainly apoptosis as shown by DNA degradation and nuclear fragmentation visualized by fluorescence microscopy after DAPI staining, changes in cell morphology observed after Giemza-May Grünwald staining and cellular membrane organization estimated by flow cytometry after Annexin V staining. As compared with either drug alone, cotreatment with STI571 and DOX induced stronger cellular responses. A low concentration of STI571 in combination with a low concentration of DOX might be tested as an alternative approach to increasing the efficacy of chemotherapy against CML.

Keywords

EN

STI571; doxorubicin; anticancer drugs; K562 cells; apoptosis; differentiation

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2007
• Volume: 54
• Issue: 4
• Pages: 839-846

Dates

published

2007

received

2007-07-09

revised

2007-09-16

accepted

2007-10-05

(unknown)

2007-10-25

Contributors

author

Justyna Jakubowska

• Department of Molecular Biology of Cancer, Medical University of Lodz, Łódź, Poland

author

Marta Stasiak

• Department of Molecular and Medical Biophysics, Medical University of Lodz, Łódź, Poland

author

Agata Szulawska

• Department of Molecular Biology of Cancer, Medical University of Lodz, Łódź, Poland

author

Andrzej Bednarek

• Department of Molecular Cancerogenesis, Medical University of Lodz, Łódź, Poland

author

Malgorzata Czyz

• Department of Molecular Biology of Cancer, Medical University of Lodz, Łódź, Poland

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