Hsp90 inhibitor NVP-AUY922 enhances radiation sensitivity of tumor cell lines under hypoxia

Cancer Biology and Therapy

Volumn 13, Issue 6, 2012, Pages 425-434

  Djuzenova, Cholpon S ^a   Blassl, Christina ^a   Roloff, Konstanze ^a   Kuger, Sebastian ^a   Katzer, Astrid ^a   Niewidok, Natalia ^a   Günther, Nadine ^a   Polat, Bülent ^a   Sukhorukov, Vladimir L ^a   Flentje, Michael ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

Cell cycle arrest; Colony survival; DNA damage; Histone H2AX; Reoxygenation

Indexed keywords

5 (2,4 DIHYDROXY 5 ISOPROPYLPHENYL) 4 (4 MORPHOLINOMETHYLPHENYL) 3 ISOXAZOLECARBOXYLIC ACID ETHYLAMIDE; CARBONATE DEHYDRATASE IX; CYCLIN DEPENDENT KINASE 1; CYCLIN DEPENDENT KINASE 4; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 90; HISTONE H2AX; PROTEIN KINASE B; RAF PROTEIN; RETINOBLASTOMA PROTEIN;

ARTICLE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE PROGRESSION; CELL CYCLE S PHASE; CELL HYPOXIA; CELL SURVIVAL; COLONY FORMING CELL; CONTROLLED STUDY; CYTOTOXICITY; DNA DAMAGE; DOWN REGULATION; GLIOBLASTOMA; HUMAN; HUMAN CELL; IONIZING RADIATION; LUNG CARCINOMA; OXYGEN SUPPLY; OXYGEN TENSION; PROTEIN EXPRESSION; PROTEIN INDUCTION; RADIOSENSITIVITY; REOXYGENATION; TUMOR CELL LINE;

CARCINOMA; CDC2 PROTEIN KINASE; CELL CYCLE; CELL HYPOXIA; CELL LINE, TUMOR; CYCLIN-DEPENDENT KINASE 4; DNA DAMAGE; GLIOBLASTOMA; HISTONES; HSP70 HEAT-SHOCK PROTEINS; HSP90 HEAT-SHOCK PROTEINS; HUMANS; ISOXAZOLES; LUNG NEOPLASMS; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-RAF; RADIATION, IONIZING; RADIATION-SENSITIZING AGENTS; RESORCINOLS;

EID: 84860254452     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.19294     Document Type: Article

References (51)

1. Endrich B, Reinhold HS, Gross JF, Intaglietta M. Tissue perfusion inhomogeneity during early tumor growth in rats. J Natl Cancer Inst 1979; 62:387-95; PMID:283271.
2. Bristow RG, Hill RP. Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer 2008; 8:180-92; PMID:18273037; http://dx.doi.org/10.1038/nrc2344.
3. Yotnda P, Wu D, Swanson AM. Hypoxic tumors and their effect on immune cells and cancer therapy. Methods Mol Biol 2010; 651:1-29; PMID:20686957; http://dx.doi.org/10.1007/978-1-60761-786-0-1.
4. Harris AL. Hypoxia - a key regulatory factor in tumour growth. Nat Rev Cancer 2002; 2:38-47; PMID:11902584; http://dx.doi.org/10.1038/nrc704.
5. Moon EJ, Brizel DM, Chi JT, Dewhirst MW. The potential role of intrinsic hypoxia markers as prognostic variables in cancer. Antioxid Redox Signal 2007; 9:1237-94; PMID:17571959; http://dx.doi.org/10.1089/ars.2007.1623.
6. Vaupel P. Hypoxia and aggressive tumor phenotype: implications for therapy and prognosis. Oncologist 2008; 13:21-6; PMID:18458121; http://dx.doi.org/10.1634/theoncologist.13-S3-21.
7. Brown JM, Giaccia AJ. The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 1998; 58:1408-16; PMID:9537241.
8. Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 2008; 8:425-37; PMID:18500244; http://dx.doi.org/10.1038/nrc2397.
9. Rohwer N, Cramer T. Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist Updat 2011; 14:191-201; PMID:21466972; http://dx.doi.org/10.1016/j.drup.2011.03.001.
10. Neckers L. Heat shock protein 90: the cancer chaperone. J Biosci 2007; 32:517-30; PMID:17536171; http://dx.doi.org/10.1007/s12038-007-0051-y.
11. Mahalingam D, Swords R, Carew JS, Nawrocki ST, Bhalla K, Giles FJ. Targeting HSP90 for cancer therapy. Br J Cancer 2009; 100:1523-9; PMID:19401686; http://dx.doi.org/10.1038/sj.bjc.6605066.
12. Workman P. Altered states: selectively drugging the Hsp90 cancer chaperone. Trends Mol Med 2004; 10:47-51; PMID:15106614; http://dx.doi.org/10. 1016/j.molmed.2003.12.005.
13. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100:57-70; PMID:10647931; http://dx.doi.org/10.1016/S0092-8674(00)81683-9.
14. Koga F, Kihara K, Neckers L. Inhibition of cancer invasion and metastasis by targeting the molecular chaperone heat-shock protein 90. Anticancer Res 2009; 29:797-807; PMID:19414312.
15. Cao X, Bloomston M, Zhang T, Frankel WL, Jia G, Wang B, et al. Synergistic antipancreatic tumor effect by simultaneously targeting hypoxic cancer cells with HSP90 inhibitor and glycolysis inhibitor. Clin Cancer Res 2008; 14:1831-9; PMID:18347186; http://dx.doi.org/10.1158/1078-0432.CCR-07-1607.
16. Bull EE, Dote H, Brady KJ, Burgan WE, Carter DJ, Cerra MA, et al. Enhanced tumor cell radiosensitivity and abrogation of G2 and S phase arrest by the Hsp90 inhibitor 17-(dimethylaminoethylamino)- 17-demethoxygeldanamycin. Clin Cancer Res 2004; 10:8077-84; PMID:15585643; http://dx.doi.org/10.1158/1078- 0432.CCR-04-1212.
17. Russell JS, Burgan W, Oswald KA, Camphausen K, Tofilon PJ. Enhanced cell killing induced by the combination of radiation and the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin: a multitarget approach to radiosensitization. Clin Cancer Res 2003; 9:3749-55; PMID:14506167.
18. Bisht KS, Bradbury CM, Mattson D, Kaushal A, Sowers A, Markovina S, et al. Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity. Cancer Res 2003; 63:8984-95; PMID:14695217.
19. Harashima K, Akimoto T, Nonaka T, Tsuzuki K, Mitsuhashi N, Nakano T. Heat shock protein 90 (Hsp90) chaperone complex inhibitor, radicicol, potentiated radiation-induced cell killing in a hormone-sensitive prostate cancer cell line through degradation of the androgen receptor. Int J Radiat Biol 2005; 81:63-76; PMID:15962764; http://dx.doi.org/10.1080/09553000400029460.
20. Wu X, Wanders A, Wardega P, Tinge B, Gedda L, Bergstrom S, et al. Hsp90 is expressed and represents a therapeutic target in human oesophageal cancer using the inhibitor 17-allylamino-17-demethoxygeldanamycin. Br J Cancer 2009; 100:334-43; PMID:19142186; http://dx.doi.org/10.1038/sj.bjc.6604855.
21. Kabakov AE, Makarova YM, Malyutina YV. Radiosensitization of human vascular endothelial cells through Hsp90 inhibition with 17-N-allilamino-17- demethoxygeldanamycin. Int J Radiat Oncol Biol Phys 2008; 71:858-65; PMID:18410996; http://dx.doi.org/10.1016/j.ijrobp.2008.02.034.
22. Machida H, Matsumoto Y, Shirai M, Kubota N. Geldanamycin, an inhibitor of Hsp90, sensitizes human tumour cells to radiation. Int J Radiat Biol 2003; 79:973-80; PMID:14713575; http://dx.doi.org/10.1080/09553000310001626135.
23. Dote H, Burgan WE, Camphausen K, Tofilon PJ. Inhibition of hsp90 compromises the DNA damage response to radiation. Cancer Res 2006; 66:9211-20; PMID:16982765; http://dx.doi.org/10.1158/0008-5472.CAN-06-2181.
24. Stingl L, Stühmer T, Chatterjee M, Jensen MR, Flentje M, Djuzenova CS. Novel HSP90 inhibitors, NVP-AUY922 and NVP-BEP800, radiosensitise tumour cells through cell cycle impairment, increased DNA damage and repair protraction. Br J Cancer 2010; 102:1578-91; PMID:20502461; http://dx.doi.org/10. 1038/sj.bjc.6605683.
25. Okui T, Shimo T, Hassan NM, Fukazawa T, Kurio N, Takaoka M, et al. Antitumor effect of novel HSP90 inhibitor NVP-AUY922 against oral squamous cell carcinoma. Anticancer Res 2011; 31:1197-204; PMID:21508365.
26. Lee KH, Lee JH, Han SW, Im SA, Kim TY, Oh DY, et al. Antitumor activity of NVP-AUY922, a novel heat shock protein 90 inhibitor, in human gastric cancer cells is mediated through proteasomal degradation of client proteins. Cancer Sci 2011; 102:1388-95; http://dx.doi.org/10.1111/j.1349-7006.2011.01944.x; PMID:21453385.
27. Tauchi T, Okabe S, Ashihara E, Kimura S, Maekawa T, Ohyashiki K. Combined effects of novel heat shock protein 90 inhibitor NVP-AUY922 and nilotinib in a random mutagenesis screen. Oncogene 2011; 30:2789-97; http://dx.doi.org/10.1038/ onc.2011.3; PMID:21278787.
28. Hammond EM, Dorie MJ, Giaccia AJ. ATR/ATM targets are phosphorylated by ATR in response to hypoxia and ATM in response to reoxygenation. J Biol Chem 2003; 278:12207-13; PMID:12519769; http://dx.doi.org/10.1074/jbc.M212360200.
29. Tanno S, Yanagawa N, Habiro A, Koizumi K, Nakano Y, Osanai M, et al. Serine/threonine kinase AKT is frequently activated in human bile duct cancer and is associated with increased radioresistance. Cancer Res 2004; 64:3486-90; PMID:15150102; http://dx.doi.org/10.1158/0008-5472.CAN-03-1788.
30. Pirollo KF, Hao Z, Rait A, Ho CW, Chang EH. Evidence supporting a signal transduction pathway leading to the radiation-resistant phenotype in human tumor cells. Biochem Biophys Res Commun 1997; 230:196-201; PMID:9020045; http://dx.doi.org/10.1006/bbrc.1996.5922.
31. Shin KH, Diaz-Gonzalez JA, Russell J, Chen Q, Burgman P, Li XF, et al. Detecting changes in tumor hypoxia with carbonic anhydrase IX and pimonidazole. Cancer Biol Ther 2007; 6:70-5; PMID:17172824; http://dx.doi.org/10.4161/cbt.6.1. 3550.
32. Kaluzová M, Pastoreková S, Pastorek J, Kaluz S. p53 tumour suppressor modulates transcription of the TATA-less gene coding for the tumour-associated carbonic anhydrase MN/CA IX in MaTu cells. Biochim Biophys Acta 2000; 1491:20-6; PMID:10760566.
33. Koll TT, Feis SS, Wright MH, Teniola MM, Richardson MM, Robles AI, et al. HSP90 inhibitor, DMAG, synergizes with radiation of lung cancer cells by interfering with base excision and ATM-mediated DNA repair. Mol Cancer Ther 2008; 7:1985-92; PMID:18645008; http://dx.doi.org/10.1158/1535-7163.MCT-07-2104.
34. Powers MV, Clarke PA, Workman P. Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis. Cancer Cell 2008; 14:250-62; PMID:18772114; http://dx.doi.org/10.1016/j.ccr.2008.08.002.
35. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 1998; 273:5858-68; PMID:9488723; http://dx.doi.org/10.1074/jbc.273.10.5858.
36. Djuzenova CS, Flentje M. Characterization of Fanconi anemia fibroblasts in terms of clonogenic survival and DNA damage assessed by the Comet assay. Med Sci Monit 2002; 8:421-30; PMID:12388916.
37. Hammond EM, Denko NC, Dorie MJ, Abraham RT, Giaccia AJ. Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol 2002; 22:1834-43; PMID:11865061; http://dx.doi.org/10.1128/MCB.22.6.1834-43.2002.
38. Massey AJ, Schoepfer J, Brough PA, Brueggen J, Chène P, Drysdale MJ, et al. Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800. Mol Cancer Ther 2010; 9:906-19; PMID:20371713; http://dx.doi.org/10.1158/1535-7163.MCT-10-0055.
39. Jensen MR, Schoepfer J, Radimerski T, Massey A, Guy CT, Brueggen J, et al. NVP-AUY922: a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models. Breast Cancer Res 2008; 10:33; PMID:18430202; http://dx.doi.org/10.1186/bcr1996.
40. McCollum AK, Lukasiewicz KB, Teneyck CJ, Lingle WL, Toft DO, Erlichman C. Cisplatin abrogates the geldanamycin-induced heat shock response. Mol Cancer Ther 2008; 7:3256-64; PMID:18852129; http://dx.doi.org/10.1158/1535-7163.MCT-08- 0157.
41. Messaoudi S, Peyrat JF, Brion JD, Alami M. Recent advances in Hsp90 inhibitors as antitumor agents. Anticancer Agents Med Chem 2008; 8:761-82; PMID:18855578.
42. Li Y, Zhang T, Schwartz SJ, Sun D. New developments in Hsp90 inhibitors as anti-cancer therapeutics: mechanisms, clinical perspective and more potential. Drug Resist Updat 2009; 12:17-27; PMID:19179103; http://dx.doi.org/ 10.1016/j.drup.2008.12.002.
43. Brough PA, Barril X, Borgognoni J, Chene P, Davies NG, Davis B, et al. Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone. J Med Chem 2009; 52:4794-809; PMID:19610616; http://dx.doi.org/10.1021/jm900357y.
44. Eccles SA, Massey A, Raynaud FI, Sharp SY, Box G, Valenti M, et al. NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis and metastasis. Cancer Res 2008; 68:2850-60; PMID:18413753; http://dx.doi.org/10.1158/0008-5472.CAN-07-5256.
45. Olive PL, Banáth JP. Phosphorylation of histone H2AX as a measure of radiosensitivity. Int J Radiat Oncol Biol Phys 2004; 58:331-5; PMID:14751500; http://dx.doi.org/10.1016/j.ijrobp.2003.09.028.
46. Bencokova Z, Kaufmann MR, Pires IM, Lecane PS, Giaccia AJ, Hammond EM. ATM activation and signaling under hypoxic conditions. Mol Cell Biol 2009; 29:526-37; PMID:18981219; http://dx.doi.org/10.1128/MCB.01301-08.
47. Djuzenova CS, Güttler T, Berger S, Katzer A, Flentje M. Differential response of human glioblastoma cell lines to combined camptothecin and ionizing radiation treatment. Cancer Biol Ther 2008; 7:364-73; PMID:18075304; http://dx.doi.org/10.4161/cbt.7.3.5363.
48. Vordermark D, Kaffer A, Riedl S, Katzer A, Flentje M. Characterization of carbonic anhydrase IX (CA IX) as an endogenous marker of chronic hypoxia in live human tumor cells. Int J Radiat Oncol Biol Phys 2005; 61:1197-207; PMID:15752902; http://dx.doi.org/10.1016/j.ijrobp.2004.11.031.
49. Muslimovic A, Ismail IH, Gao Y, Hammarsten O. An optimized method for measurement of gamma-H2AX in blood mononuclear and cultured cells. Nat Protoc 2008; 3:1187-93; PMID:18600224; http://dx.doi.org/10.1038/nprot.2008.93.
50. Mahrhofer H, Bürger S, Oppitz U, Flentje M, Djuzenova CS. Radiation induced DNA damage and damage repair in human tumor and fibroblast cell lines assessed by histone H2AX phosphorylation. Int J Radiat Oncol Biol Phys 2006; 64:573-80; PMID:16414372; http://dx.doi.org/10.1016/j.ijrobp.2005.09.037.
51. Djuzenova CS, Sukhorukov VL, Klöck G, Arnold WM, Zimmermann U. Effect of electric field pulses on the viability and on the membrane-bound immunoglobulins of LPS-activated murine B-lymphocytes: correlation with the cell cycle. Cytometry 1994; 15:35-45; PMID:8162823; http://dx.doi.org/10.1002/cyto. 990150107.