Staurosporine modulates radiosensitivity and radiation-induced apoptosis in U937 cells.
OBJECTIVE
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.


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.
Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, Tainan, Taiwan.
How-Ran
HR
Guo
Chia-Hsin
CH
Chen
Sheng-Yow
SY
Ho
Yuan-Soon
YS
Ho
Rong-Jane
RJ
Chen
Ying-Jan
YJ
Wang
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006801:Humans; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D019311:Staurosporine / Q000008:administration & dosage*; D020298:U937 Cells
D018797:Cell Cycle Proteins; D011838:Radiation-Sensitizing Agents; D019311:Staurosporine