The importance of abrogation of G2-phase arrest in combined effect of TRAIL and ionizing radiation

• Authors: Martina Řezáčová , Jiřina Vávrová , Doris Vokurková , Aleš Tichý , Jiří Knížek , Jan Psutka
• Languages of publication: EN

Abstracts

EN

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 G2 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 µg/l TRAIL for 16 h reduced D0 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 µg/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.

Keywords

EN

ionizing radiation; TRAIL; DR5 receptor; apoptosis; HL-60 cells

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2005
• Volume: 52
• Issue: 4
• Pages: 889-895

Dates

published

2005

received

2004-12-13

revised

2005-02-15

accepted

2005-05-06

(unknown)

2005-07-11

Contributors

author

Martina Řezáčová

• Institute of Medical Biochemistry, Faculty of Medicine Hradec Králové, Charles University Prague, Hradec Králové, Czech Republic

author

Jiřina Vávrová

• Department of Radiobiology, School of Military Health Sciences, Hradec Králové, University of Defence Brno, Hradec Králové, Czech Republic

author

Doris Vokurková

• Institute of Clinical Immunology and Allergology, University Hospital, Hradec Králové, Czech Republic

author

Aleš Tichý

• Institute of Medical Biochemistry, Faculty of Medicine Hradec Králové, Charles University Prague, Hradec Králové, Czech Republic

author

Jiří Knížek

• Institute of Medical Biophysics, Faculty of Medicine Hradec Králové, Charles University Prague, Hradec Králové, Czech Republic

author

Jan Psutka

• Department of Military Medical Service Organization, School of Military Health Sciences, Hradec Králové, University of Defence Brno, Hradec Králové, Czech Republic

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