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.
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 24h 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 apoptosis induction; however Wee1 681641 increased ionizing radiation-induced cell death in MOLT-4 cells.
authors.affiliation: Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, Pardubice 532 10, Czech Republic. Electronic address: radim.havelek@upce.cz.
authors.forename: Radim
authors.initials: R
authors.lastname: Havelek
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Simkova 870, Hradec Kralove 500 38, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Cmielova
authors.affiliation: Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, Pardubice 532 10, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Kralovec
authors.affiliation: Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, Pardubice 532 10, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Bruckova
authors.affiliation: Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, Pardubice 532 10, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Bilkova
authors.affiliation: Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, Pardubice 532 10, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Fousova
authors.affiliation: Department of Radiobiology, Faculty of Military Health Sciences, University of Defence in Brno, Trebesska 1575, Hradec Kralove 500 01, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Sinkorova
authors.affiliation: Department of Radiobiology, Faculty of Military Health Sciences, University of Defence in Brno, Trebesska 1575, Hradec Kralove 500 01, Czech Republic.
authors.forename: Jirina
authors.initials: J
authors.lastname: Vavrova
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Simkova 870, Hradec Kralove 500 38, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Rezacova
mesh_terms: D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051135:Rad51 Recombinase / Q000037:antagonists & inhibitors*; D011839:Radiation, Ionizing
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D051135:Rad51 Recombinase
keywords: Apoptosis; Ionizing radiation; T-cell leukemic cells; γH2AX