Changes in the response of MCF-7 cells to ionizing radiation after the combination of ATM and DNA-PK inhibition
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- ATM protein antagonisté a inhibitory metabolismus MeSH
- buněčná smrt účinky léků MeSH
- checkpoint kinasa 1 MeSH
- checkpoint kinasa 2 metabolismus MeSH
- chromony farmakologie MeSH
- DNA vazebné proteiny antagonisté a inhibitory MeSH
- G1 fáze účinky léků MeSH
- G2 fáze účinky léků MeSH
- histony MeSH
- inhibitor p21 cyklin-dependentní kinasy metabolismus MeSH
- ionizující záření MeSH
- kontrolní body buněčného cyklu účinky léků MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- morfoliny farmakologie MeSH
- nádorové buněčné linie MeSH
- oprava DNA účinky léků MeSH
- poškození DNA účinky léků MeSH
- proteinkinasa aktivovaná DNA antagonisté a inhibitory metabolismus MeSH
- proteinkinasy metabolismus MeSH
- protokoly protinádorové kombinované chemoterapie farmakologie MeSH
- pyrony farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one MeSH Prohlížeč
- 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one MeSH Prohlížeč
- ATM protein, human MeSH Prohlížeč
- ATM protein MeSH
- CDKN1A protein, human MeSH Prohlížeč
- checkpoint kinasa 1 MeSH
- checkpoint kinasa 2 MeSH
- CHEK1 protein, human MeSH Prohlížeč
- CHEK2 protein, human MeSH Prohlížeč
- chromony MeSH
- DNA vazebné proteiny MeSH
- H2AX protein, human MeSH Prohlížeč
- histony MeSH
- inhibitor p21 cyklin-dependentní kinasy MeSH
- morfoliny MeSH
- proteinkinasa aktivovaná DNA MeSH
- proteinkinasy MeSH
- pyrony MeSH
The aim of the present study is to evaluate the role of ATM (KU55933) and DNA-PK (NU7441) inhibitors in the repair of double-strand breaks and downstream signaling of DNA damage introduced by ionizing radiation. The irradiation of MCF-7 cells alone increased the proportion of cells in the G1 phase in comparison with mock-treated cells. After ATM inhibitor pretreatment, the cells were more accumulated in the G2 phase, whereas DNA-PK inhibitor application increased the percentage of cells in the G1 phase. ATM and DNA-PK inhibitor application alone increased the sensitivity of MCF-7 cells to ionizing radiation; however, combining both inhibitors together resulted in a further enhancement of cell death. Unexpectedly, combining both inhibitors decreased the percentage of senescent cells and increased G2 cell cycle arrest 3 days after treatment. After irradiation, the p21 protein was increased and Chk1 and Chk2 were activated. These proteins were not increased in cells pretreated with the ATM inhibitor prior to ionizing radiation exposure, albeit DNA-PK inhibitor application did not affect the amount of proteins detected. Formation of γH2AX was found to be ATM and DNA-PK dependent, application of the ATM inhibitor suppressed incidence of γH2AX, whereas DNA-PK caused persistence of γH2AX. Our results suggest that the further investigation of the ATM inhibitor in combination with the DNA-PK inhibitor as sensitizers preventing cell senescence and promoting cell death in breast carcinoma MCF-7 cells is warranted.
Zobrazit více v PubMed
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