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) 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.

• Authors: How-Ran Guo, Chia-Hsin Chen, Sheng-Yow Ho, Yuan-Soon Ho, Rong-Jane Chen, Ying-Jan Wang
• Journal: International journal of radiation biology (Int J Radiat Biol) Vol. 82 Issue 2 Pg. 97-109 (Feb 2006) ISSN: 0955-3002 [Print] England
• PMID: 16546908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• Radiation-Sensitizing Agents
• Staurosporine

Topics

• Apoptosis (drug effects, radiation effects)
• Cell Cycle (drug effects, radiation effects)
• Cell Cycle Proteins (metabolism)
• Humans
• Radiation Tolerance (drug effects)
• Radiation-Sensitizing Agents (administration & dosage)
• Staurosporine (administration & dosage)
• U937 Cells