Radio-sensitization of human leukaemic molt-4 cells by DNA-dependent protein kinase inhibitor, NU7026
| Autor: | Lenka Zárybnická, Zuzana Šinkorová, Barbora Salovska, Eva Novotná, Jaroslav Pejchal, Radka Sedlaříková, Jiřina Vávrová, Kamila Ďurišová, Aleš Tichý, Martina Řezáčová |
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| Rok vydání: | 2012 |
| Předmět: |
Ionizing radiation
Radiation-Sensitizing Agents Leukemia T-Cell DNA Repair DNA damage DNA repair Morpholines lcsh:Medicine Apoptosis DNA-Activated Protein Kinase Radiation Tolerance DNA-PK Cell Line Tumor Histone H2A PI3-K Leukaemia Humans Viability assay Protein kinase A Inhibitor NU7026 Cell Proliferation Chemistry lcsh:R Cell Cycle General Medicine Cell cycle Molecular biology Blot Chromones Gamma Rays ATM DNA Damage |
| Zdroj: | Acta Medica, Vol 55, Iss 2, Pp 66-73 (2012) |
| ISSN: | 1211-4286 |
| Popis: | In this paper we describe the influence of NU7026, a specific inhibitor of DNA-dependent protein kinase, phosphoinositide 3-kinase, and ATM-kinase on molecular and cellular mechanisms triggered by ionising irradiation in human T-lymphocyte leukaemic MOLT-4 cells. We studied the effect of this inhibitor (10 μM) combined with gammaradiation (1 Gy) leading to DNA damage response and induction of apoptosis. We used methods for apoptosis assessment (cell viability count and flow-cytometric analysis) and cell cycle analysis (DNA content measurement) and we detected expression and post-translational modifications (Western blotting) of proteins involved in DNA repair signalling pathways. Pre-treatment with NU7026 resulted into decreased activation of checkpoint kinase-2 (Thr68), p53 (Ser15 and Ser392), and histone H2A.X (Ser139) 2 hours after irradiation. Subsequently, combination of radiation and inhibitor led to decreased amount of cells in G2-phase arrest and into increased apoptosis after 72 hours. Our results indicate that in leukaemic cells the pre-incubation with inhibitor NU7026 followed by low doses of ionising radiation results in radio-sensitising of MOLT-4 cells via diminished DNA repair and delayed but pronounced apoptosis. This novel approach might offer new strategies in combined treatment of leukaemia diseases. |
| Databáze: | OpenAIRE |
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