TY - JOUR
T1 - Staurosporine modulates radiosensitivity and radiation-induced apoptosis in U937 cells
AU - Guo, How Ran
AU - Chen, Chia Hsin
AU - Ho, Sheng Yow
AU - Ho, Yuan Soon
AU - Chen, Rong Jane
AU - Wang, Ying Jan
N1 - Funding Information:
This study was supported by the National Science Council (NSC 93-2320-B-006-031 and NSC 93-2320-B-006-049).
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
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U2 - 10.1080/09553000600589149
DO - 10.1080/09553000600589149
M3 - Article
C2 - 16546908
AN - SCOPUS:33645166806
SN - 0955-3002
VL - 82
SP - 97
EP - 109
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
IS - 2
ER -