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

Biochem Biophys Res Commun. 2014 Oct 24;453(3):569-75. doi: 10.1016/j.bbrc.2014.09.123. Epub 2014 Oct 5.

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.

Keywords: Apoptosis; Ionizing radiation; T-cell leukemic cells; γH2AX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / antagonists & inhibitors*
  • DNA Damage / radiation effects*
  • DNA Repair
  • Humans
  • Jurkat Cells
  • Leukemia, T-Cell / enzymology*
  • Leukemia, T-Cell / genetics
  • Leukemia, T-Cell / pathology
  • Nuclear Proteins / antagonists & inhibitors*
  • Protein Kinase Inhibitors / pharmacology
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Rad51 Recombinase / antagonists & inhibitors*
  • Radiation, Ionizing

Substances

  • Cell Cycle Proteins
  • Nuclear Proteins
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • WEE1 protein, human
  • Rad51 Recombinase