Staurosporine modulates radiosensitivity and radiation-induced apoptosis in U937 cells

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) NH₂-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.

Keywords:

• Apoptosis
• cell cycle checkpoints
• chemical modifiers
• leukaemias
• radiotherapy