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

• Published in: Biochemical and biophysical research communications Vol. 453; no. 3; pp. 569 - 575
• Main Authors: Havelek, Radim, Cmielova, Jana, Kralovec, Karel, Bruckova, Lenka, Bilkova, Zuzana, Fousova, Ivana, Sinkorova, Zuzana, Vavrova, Jirina, Rezacova, Martina
• Format: Journal Article
• Language: English
• Published: United States 24-10-2014
• Subjects: 60 APPLIED LIFE SCIENCES; APOPTOSIS; BIOLOGICAL RADIATION EFFECTS; CELL CYCLE; Cell Cycle Proteins - antagonists & inhibitors; DNA Damage - radiation effects; DNA Repair; HUMAN POPULATIONS; Humans; INHIBITION; IONIZING RADIATIONS; IRRADIATION; Jurkat Cells; Leukemia, T-Cell - enzymology; Leukemia, T-Cell - genetics; Leukemia, T-Cell - pathology; MOLECULES; NEOPLASMS; Nuclear Proteins - antagonists & inhibitors; PATIENTS; PHOSPHOTRANSFERASES; Protein Kinase Inhibitors - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Rad51 Recombinase - antagonists & inhibitors; Radiation, Ionizing; RADIOTHERAPY; REPAIR; SENSITIVITY; STRAND BREAKS; T-cell leukemic cells; Ionizing radiation; γH2AX; Apoptosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.09.123

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.