Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60)

0399421 - BFÚ 2014 RIV US eng J - Článek v odborném periodiku
Vávrová, J. - Zárybnická, L. - Lukášová, Emilie - Řezáčová, M. - Novotná, E. - Šinkorová, Z. - Tichý, Adam - Pejchal, J. - Ďurišová, K.
Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60).
Radiation and Environmental Biophysics. Roč. 52, č. 4 (2013), s. 471-479. ISSN 0301-634X. E-ISSN 1432-2099
Institucionální podpora: RVO:68081707
Klíčová slova: DOUBLE-STRAND BREAKS * GAMMA-RADIATION * CANCER-CELLS
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 1.582, rok: 2013

We compared the effects of inhibitors of kinases ATM (KU55933) and ATR (VE-821) (incubated for 30 min before irradiation) on the radiosensitization of human promyelocyte leukaemia cells (HL-60), lacking functional protein p53. VE-821 reduces phosphorylation of check-point kinase 1 at serine 345, and KU55933 reduces phosphorylation of check-point kinase 2 on threonine 68 as assayed 4 h after irradiation by the dose of 6 Gy. Within 24 h after gamma-irradiation with a dose of 3 Gy, the cells accumulated in the G2 phase (67 %) and the number of cells in S phase decreased. KU55933 (10 mu M) did not affect the accumulation of cells in G2 phase and did not affect the decrease in the number of cells in S phase after irradiation. VE-821 (2 and 10 mu M) reduced the number of irradiated cells in the G2 phase to the level of non-irradiated cells and increased the number of irradiated cells in S phase, compared to irradiated cells not treated with inhibitors. In the 144 h interval after irradiation with 3 Gy, there was a considerable induction of apoptosis in the VE-821 group (10 mu M).
Trvalý link: http://hdl.handle.net/11104/0226767