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

Journal Article · Fri Oct 24 04:00:00 EDT 2014 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2014.09.123· OSTI ID:22416802

Havelek, Radim ^[1]; Cmielova, Jana ^[2]; Kralovec, Karel; Bruckova, Lenka; Bilkova, Zuzana; Fousova, Ivana ^[1]; Sinkorova, Zuzana; Vavrova, Jirina ^[3]; Rezacova, Martina ^[2]

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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)

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 apoptosis induction; however Wee1 681641 increased ionizing radiation-induced cell death in MOLT-4 cells.

• OSTI ID: 22416802
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 453; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

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