The importance of abrogation of G2-phase arrest in combined effect of TRAIL and ionizing radiation
Language English Country Switzerland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16025160
PII: 20051032
Knihovny.cz E-resources
- MeSH
- Cell Cycle drug effects radiation effects MeSH
- G2 Phase drug effects physiology radiation effects MeSH
- HL-60 Cells MeSH
- Humans MeSH
- Membrane Glycoproteins pharmacology MeSH
- TNF-Related Apoptosis-Inducing Ligand MeSH
- Apoptosis Regulatory Proteins pharmacology MeSH
- Receptors, Tumor Necrosis Factor physiology radiation effects MeSH
- Tumor Necrosis Factor-alpha pharmacology MeSH
- Receptors, TNF-Related Apoptosis-Inducing Ligand MeSH
- Dose-Response Relationship, Radiation MeSH
- Gamma Rays MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Membrane Glycoproteins MeSH
- TNF-Related Apoptosis-Inducing Ligand MeSH
- Apoptosis Regulatory Proteins MeSH
- Receptors, Tumor Necrosis Factor MeSH
- Tumor Necrosis Factor-alpha MeSH
- TNFRSF10B protein, human MeSH Browser
- TNFSF10 protein, human MeSH Browser
- Receptors, TNF-Related Apoptosis-Inducing Ligand MeSH
BACKGROUND: In this work we studied the relationship between the enhanced expression of DR5 receptor and the effect of combination of TRAIL and ionizing radiation on cell cycle arrest and apoptosis induction in human leukemia cell line HL-60. MATERIAL AND METHODS: DR5, APO2.7 and cell cycle were analyzed by flow cytometry. Proteins Bid and Mcl-1 were analyzed by Western-blotting. For clonogenic survival, colony assay on methylcellulose was used. RESULTS: Ionizing radiation caused significantly enhanced positivity of DR5 receptors 24 h after irradiation with high doses (6 and 8 Gy). An increase of DR5 receptor positivity after a dose of 2 Gy was not statistically significant and application of TRAIL 48 h after irradiation did not increase the apoptosis induction. However, a decrease of radiation-induced G(2) phase arrest and an increase of apoptosis were observed when TRAIL was applied 16 h before irradiation with the dose of 2 Gy. Incubation with 6 microg/l TRAIL for 16 h reduced D(0) value from 2.9 Gy to 1.5 Gy. The induction of apoptosis by TRAIL was accompanied by Bid cleavage and a decrease of antiapoptotic Mcl-1 16 h after incubation with TRAIL. CONCLUSION: TRAIL in concentration of 6 microg/l applied 16 h before irradiation by the dose of 1.5 Gy caused the death of 63% of clonogenic tumor cells, similarly as the dose of 2.9 Gy alone, which is in good correlation with the enhanced apoptosis induction.
