The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia
Abstract
We report for the first time the use of a selective small-molecule inhibitor of DNA repair to potentiate topoisomerase II (topo II) poisons, identifying DNA-dependent protein kinase (DNA-PK) as a potential target for leukemia therapy. Topo II poisons form cleavable complexes that are processed to DNA double-strand breaks (DSBs). DNA-PK mediates nonhomologous end joining (NHEJ). Inhibition of this DSB repair pathway may sensitize cells to topo II poisons. We investigated the effects of a novel DNA-PK inhibitor, NU7026 (2-(morpholin-4-yl)-benzo[h]chomen-4-one), on the response to topo II poisons using K562 leukemia cells. NU7026 (10 μM) potentiated the growth inhibition of idarubicin, daunorubicin, doxorubicin, etoposide, amsacrine (mAMSA), and mitroxantrone with potentiation factors at 50% growth inhibition ranging from approximately 19 for mAMSA to approximately 2 for idarubicin (potentiation of etoposide was confirmed by clonogenic assay). In contrast, NU7026 did not potentiate camptothecin or cytosine arabinoside (araC). NU7026 did not affect the levels of etoposide-induced topo IIα or β cleavable complexes. NU7026 alone had no effect on cell cycle distribution, but etoposide-induced accumulation in G2/M was increased by NU7026. A concentration-dependent increase in etoposide-induced DSB levels was increased by NU7026. The mechanism of NU7026 potentiation of topo II poisons involves inhibition of NHEJ and a G2/M checkpoint arrest. (Blood. 2004;103:4659-4665)
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Cites
Ma, Y., Pannicke, U., Schwarz, K., & Lieber, M. R. (2002) · Cell · doi:10.1016/s0092-8674(02)00671-2 · Cited by 1,166
Sensing and repairing DNA double-strand breaks
Jackson, S. P. (2002) · Carcinogenesis · doi:10.1093/carcin/23.5.687 · Cited by 1,128
The DNA-dependent protein kinase
Smith, G. C. M., & Jackson, S. P. (1999) · Genes & Development · doi:10.1101/gad.13.8.916 · Cited by 887
ATM and ATR: networking cellular responses to DNA damage
Shiloh, Y. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00159-3 · Cited by 601
DNA end-joining: from yeast to man
Critchlow, S. E., & Jackson, S. P. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01284-5 · Cited by 584
Bradley, M. O., & Kohn, K. W. (1979) · Nucleic Acids Research · doi:10.1093/nar/7.3.793 · Cited by 563
DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme?
Durocher, D., & Jackson, S. P. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00201-5 · Cited by 500
Yang, S. W., Burgin, A. B., Huizenga, B. N., Robertson, C. A., Yao, K. C., & Nash, H. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.21.11534 · Cited by 412
Gu, Y., Jin, S., Gao, Y., Weaver, D. T., & Alt, F. W. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.8076 · Cited by 408
Veuger, S. J., Curtin, N. J., Richardson, C. J., Smith, G. C. M., & Durkacz, B. W. (2003) · PubMed · doi:10.25405/ncl.34607331 · Cited by 328
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Cited by
DNA repair dysregulation from cancer driver to therapeutic target
Curtin, N. J. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3399 · Cited by 1,051
The DNA Damage Response: Implications for Tumor Responses to Radiation and Chemotherapy
Goldstein, M., & Kastan, M. B. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-081313-121208 · Cited by 590
Toledo, L. I., Murga, M., Zur, R., Soria, R., Rodriguez, A., Martinez, S., Oyarzabal, J., Pastor, J., Bischoff, J. R., & Fernandez-Capetillo, O. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2076 · Cited by 465
Leahy, J. J. J., Golding, B. T., Griffin, R. J., Hardcastle, I. R., Richardson, C., Rigoreau, L., & Smith, G. C. M. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.09.060 · Cited by 411
Fok, J. H. L., Ramos-Montoya, A., Vazquez-Chantada, M., Wijnhoven, P. W. G., Follia, V., James, N., Farrington, P. M., Karmokar, A., Willis, S. E., Cairns, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12836-9 · Cited by 331
Metadata
- Authors
- Willmore, E., de Caux, S., Sunter, N. J., Tilby, M. J., Jackson, G. H., Austin, C. A., & Durkacz, B. W.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2004-06-15
- Volume
- 103
- Issue
- 12
- Pages
- 4659-4665
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2024254896
- Cited by
- 273
- References
- 33
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- closed
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- Willmore, E., de Caux, S., Sunter, N. J., Tilby, M. J., Jackson, G. H., Austin, C. A., & Durkacz, B. W. (2004). A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia. Blood. https://doi.org/10.1182/blood-2003-07-2527
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