Abstract
Purpose: The present study aims at investigating the involvement of several genes in the cell cycle distribution and apoptosis in U937 cells, a cell line lacking functional p53 protein, after combined treatment with staurosporine and irradiation. Materials and methods: Using a DNA fragmentation assay, flow cytometry and western blot analysis, the molecular basis for the effects of staurosporine in combination with the irradiation of leukemia cells was investigated. Results: Our results indicated that combined treatment led to an increased apoptotic cell death in U937 cells, which is correlated with the phosphorylation of the V-Jun sarcoma virus 17 oncogene homolog (c-JUN) NH 2-terminal kinase protein (JNK), the activation of caspases, the increase in B cell leukemia/lymphoma 2 (Bcl-2) associated X protein (Bax), the decrease in Bcl xL protein (Bcl-XL) levels, the loss of mitochondria membrane potential and the release of cytochrome c. Conclusions: Abrogation of the G2 checkpoint should be an effective strategy against p53-deficient leukemia cells to irradiation-induced cell killing.
Original language | English |
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Pages (from-to) | 97-109 |
Number of pages | 13 |
Journal | International Journal of Radiation Biology |
Volume | 82 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb 2006 |
Keywords
- Apoptosis
- Cell cycle checkpoints
- Chemical modifiers
- Leukaemias
- Radiotherapy
ASJC Scopus subject areas
- Radiological and Ultrasound Technology
- Radiology Nuclear Medicine and imaging