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Title: Specific inhibition of Wee1 kinase and Rad51 recombinase: A strategy to enhance the sensitivity of leukemic T-cells to ionizing radiation-induced DNA double-strand breaks

Highlights: • Pre-treatment with the inhibitors increased the sensitivity of Jurkat cells to irradiation. • Combining both inhibitors together resulted in a G2 cell cycle arrest abrogation in Jurkat. • Jurkat cells pre-treated with inhibitors were positive for γH2AX foci 24 h upon irradiation. • Pre-treatment with Rad51 RI-1 had no effect on apoptosis induction in MOLT-4 cells. • When dosed together, the combination decreased MOLT-4 cell survival. - Abstract: Present-day oncology sees at least two-thirds of cancer patients receiving radiation therapy as a part of their anticancer treatment. The objectives of the current study were to investigate the effects of the small molecule inhibitors of Wee1 kinase II (681641) and Rad51 (RI-1) on cell cycle progression, DNA double-strand breaks repair and apoptosis following ionizing radiation exposure in human leukemic T-cells Jurkat and MOLT-4. Pre-treatment with the Wee1 681641 or Rad51 RI-1 inhibitor alone increased the sensitivity of Jurkat cells to irradiation, however combining both inhibitors together resulted in a further enhancement of apoptosis. Jurkat cells pre-treated with inhibitors were positive for γH2AX foci 24 h upon irradiation. MOLT-4 cells were less affected by inhibitors application prior to ionizing radiation exposure. Pre-treatment with Rad51 RI-1 had no effect on apoptosismore » induction; however Wee1 681641 increased ionizing radiation-induced cell death in MOLT-4 cells.« less
Authors:
 [1] ;  [2] ; ; ; ;  [1] ; ;  [3] ;  [2]
  1. Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, Pardubice 532 10 (Czech Republic)
  2. Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Simkova 870, Hradec Kralove 500 38 (Czech Republic)
  3. Department of Radiobiology, Faculty of Military Health Sciences, University of Defence in Brno, Trebesska 1575, Hradec Kralove 500 01 (Czech Republic)
Publication Date:
OSTI Identifier:
22416802
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 453; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BIOLOGICAL RADIATION EFFECTS; CELL CYCLE; HUMAN POPULATIONS; INHIBITION; IONIZING RADIATIONS; IRRADIATION; MOLECULES; NEOPLASMS; PATIENTS; PHOSPHOTRANSFERASES; RADIOTHERAPY; REPAIR; SENSITIVITY; STRAND BREAKS