Effects of the novel DNA dependent protein kinase inhibitor, IC486241, on the DNA damage response to doxorubicin and cisplatin in breast cancer cells

Investigational New Drugs

Volumn 30, Issue 4, 2012, Pages 1736-1742

  Davidson, David ^a   Grenier, Jeremy ^a   Martinez Marignac, Veronica ^a   Amrein, Lilian ^a   Shawi, May ^a   Tokars, Marc ^b   Aloyz, Raquel ^a   Panasci, Lawrence ^a  

^a MCGILL UNIVERSITY   (Canada)

^b Luitpold Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CISPLATIN; DNA; DNA FRAGMENT; DOXORUBICIN; HISTONE H2AX; IC 486241; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; SERINE; SULFORHODAMINE B; UNCLASSIFIED DRUG;

ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE S PHASE; CHEMOSENSITIZATION; COMET ASSAY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA DAMAGE; DNA END JOINING REPAIR; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG POTENTIATION; DRUG STRUCTURE; ENZYME PHOSPHORYLATION; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; MOLECULAR MECHANICS; PRIORITY JOURNAL;

ACRIDONES; BREAST NEOPLASMS; CELL CYCLE; CELL LINE, TUMOR; CISPLATIN; COMET ASSAY; DIMETHYL SULFOXIDE; DNA DAMAGE; DNA, NEOPLASM; DOXORUBICIN; DRUG SCREENING ASSAYS, ANTITUMOR; DRUG SYNERGISM; FEMALE; FLOW CYTOMETRY; HUMANS; INHIBITORY CONCENTRATION 50; PROTEIN KINASE INHIBITORS; QUINAZOLINES;

EID: 84866736846     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-011-9678-5     Document Type: Article

References (28)

1. Cardoso F, Bedard PL, Winer EP, Pagani O, Senkus-Konefka E, Fallowfield LJ, Kyriakides S, Costa A, Cufer T, Albain KS, Force obotE-MT (2009) International guidelines for management of metastatic breast cancer: combination vs. sequential single-agent chemotherapy. J Natl Cancer Inst 101(17):1174-1181. doi:10.1093/jnci/djp235
2. Rabik CA, Dolan ME (2007) Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev 33(1):9-23
3. Tewey K, Rowe T, Yang L, Halligan B, Liu L (1984) Adriamycininduced DNA damage mediated bymammalian DNA topoisomerase II. Science 226(4673):466-468. doi:10.1126/science.6093249
4. Kuo CC, Liu JF, Chang JY (2006) DNA repair enzyme, O6-methylguanine DNA methyltransferase, modulates cytotoxicity of camptothecin-derived topoisomerase I inhibitors. J Pharmacol Exp Ther 316(2):946-954. doi:10.1124/jpet.105.095919
5. MansourWY, Schumacher S, Rosskopf R, Rhein T, Schmidt-Petersen F, Gatzemeier F, Haag F, Borgmann K, Willers H, Dahm-Daphi J (2008) Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks. Nucleic Acids Res 36(12):4088-4098
6. Cowell I, Durkacz B, Tilby M (2005) Sensitization of breast carcinoma cells to ionizing radiation by small molecule inhibitors of DNA-dependent protein kinase and ataxia telangiectsia mutated. Biochem Pharmacol 71:13-20
7. Dejmek J, Iglehart JD, Lazaro J-B (2009) DNA-dependent protein kinase (DNA-PK)-dependent cisplatin-induced loss of nucleolar facilitator of chromatin transcription (FACT) and regulation of cisplatin sensitivity by DNA-PK and FACT. Mol Cancer Res 7 (4):581-591
8. Willmore E, Elliott SL, Mainou-Fowler T, Summerfield GP, Jackson GH, O'Neil F, Lowe C, Carter A, Harris R, Pettitt AR, Cano-Soumillac C, Griffin RJ, Cowell IG, Austin CA, Durkacz BW (2008) DNA-dependent protein kinase is a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia. Clin Cancer Res 14(12):3984-3992
9. Willmore E, de Caux S, Sunter NJ, Tilby MJ, Jackson GH, Austin CA, Durkacz BW (2004) A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia. Blood 103:4659-4665
10. Shinohara ET, Geng L, Tan J, Chen H, Shir Y, Edwards E, Halbrook J, Kesicki EA, Kashishian A, Hallahan DE (2005) DNA-dependent protein kinase is a molecular target for the development of noncytotoxic rediation-sensitizing drugs. Cancer Res 65(12):4987-4992
11. Davidson D, Coulombe Y, Martinez-Marignac V, Amrein L, Grenier J, Hodkinson K, Masson J-Y, Aloyz R, Panasci L (2011) Irinotecan and DNA-PKcs inhibitors synergize in killing of colon cancer cells. Invest New Drugs: 1-9. doi:10.1007/s10637-010-9626-9
12. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe J-P, Tong F, Speed T, Spellman PT, DeVries S, Lapuk A, Wang NJ, Kuo W-L, Stilwell JL, Pinkel D, Albertson DG, Waldman FM, McCormick F, Dickson RB, Johnson MD, Lippman M, Ethier S, Gazdar A, Gray JW (2006) A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 10(6):515-527
13. Elstrodt F, Hollestelle A, Nagel JHA, Gorin M, Wasielewski M, van den Ouweland A, Merajver SD, Ethier SP, Schutte M (2006) BRCA1 mutation analysis of 41 human breast cancer cell lines reveals three new deleterious mutants. Cancer Res 66(1):41-45. doi:10.1158/0008-5472.can-05-2853
14. Vichai V, Kirtikara K (2006) Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc 1(3):1112-1116
15. Berenbaum M (1992) Letter correspondence re: "Greco et al., applications of a new approach for the quantitation of drug synergism to the combination of c/s-diamminedichloroplatinum and 1-tf-d-arabinofuranosylcytosine. Cancer res., 50: 5318-5327, 1990". Cancer Res 52:4558-4565
16. Amrein L, Loignon M, Goulet A-C, DunnM, Jean-Claude B, Aloyz R, Panasci L (2007) Chlorambucil cytotoxicity in malignant B lymphocytes is synergistically increased by 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026)-mediated inhibition of DNA double-strand break repair via inhibition of DNA-dependent protein kinase. J Pharmacol Exp Ther 321(3):848-855. doi:10.1124/jpet.106.118356
17. Olive PL, Banath JP (2006) The comet assay: a method to measure DNA damage in individual cells. Natl Protoc 1(1):23-29
18. Loignon M, Amrein L, Dunn M, Aloyz R (2007) Xrcc3 depletion induces spontaneous DNA breaks and p53-dependent. Cell Cycle 6(5):606-611
19. Yang J, Yingnian Y, Hamrick HE, Duerksen-Hughes J (2003) ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses. Carcinogenesis 24(10):1571-1580
20. Yang C, Betti C, Singh S, Toor A, Vaughan A (2009) Impaired NHEJ function in multiple myeloma. Mutat Res 660:66-73
21. Lord CJ, Ashworth A (2009) Bringing DNA repair in tumors into focus. Clin Cancer Res 15(10):3241-3243
22. Kao J, Rosenstein BS, Peters S, Milano MT, Kron SJ (2005) Cellular response to DNA damage. Ann NYAcad Sci 1066:243-258
23. Durocher D, Jackson PJ (2001) DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme? Curr Opin Cell Biol 13:225-231
24. Bennardo N, Cheng A, Huang N, Stark JM(2008) Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair. PLoS Genet 4(6):e1000110
25. Shrivastav M, Miller CA, de Haro LP, Durant ST, Chen BPC, Chen DJ, Nickoloff JA (2009) DNA-PKcs and ATM co-regulate DNA double-strand break repair. DNA Repair 8:920-929
26. Park E-J, Chan DW, Park J-H, Oettinger MA, Jongbum K (2003) DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner. Nucleic Acids Res 31(23):6819-6827
27. Nutley BP, Smith NF, Hayes A, Kelland LR, Brunton L, Golding BT, Smith GCM, Martin NMB, Workman P, Raynaud FI (2005) Preclinical pharmacokinetics and metabolism of a novel prototype DNA-PK inhibitor NU7026. Br J Cancer 93 (10):1011-1018
28. Stiff T, O'Driscoll M, Rief N, Iwabuchi K, Lobrich M, Jeggo PA (2004) ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res 64:2390-2396