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

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 progres...

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Bibliographic Details
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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-291X 1090-2104
DOI:	10.1016/j.bbrc.2014.09.123