Small molecule BMH-compounds that inhibit RNA polymerase I and cause nucleolar stress

Molecular Cancer Therapeutics

Volumn 13, Issue 11, 2014, Pages 2537-2546

  Peltonen, Karita ^a   Colis, Laureen ^b,d   Liu, Hester ^b   Jäämaa, Sari ^a   Zhang, Zhewei ^b,e   Hällström, Taija Af ^a   Moore, Henna M ^a,f   Sirajuddin, Paul ^b   Laiho, Marikki ^a,b,c  

^a UNIVERSITY OF HELSINKI   (Finland)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c JOHNS HOPKINS UNIVERSITY   (United States)

^d YALE UNIVERSITY   (United States)

^e ZHEJIANG UNIVERSITY   (China)

^f UNIVERSITY OF HELSINKI   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BMH 21; BMH 22; BMH 23; BMH 9; DNA DIRECTED RNA POLYMERASE; PROTEASOME; PROTEIN P53; RIBOSOME RNA; UNCLASSIFIED DRUG; ENZYME INHIBITOR; MOLECULAR LIBRARY;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BIOLOGICAL ACTIVITY; CANCER CELL LINE; CONTROLLED STUDY; EX VIVO STUDY; HUMAN; HUMAN CELL; HUMAN TISSUE; MALE; NCI60 CANCER CELL LINE; NUCLEOLAR STRESS; PROSTATE; RNA SYNTHESIS; STRESS; ANTAGONISTS AND INHIBITORS; BONE NEOPLASMS; DRUG EFFECTS; HCT116 CELL LINE; MELANOMA; MOLECULAR LIBRARY; NUCLEOLUS; OSTEOSARCOMA; PHARMACOLOGY; TUMOR CELL LINE;

BONE NEOPLASMS; CELL LINE, TUMOR; CELL NUCLEOLUS; ENZYME INHIBITORS; HCT116 CELLS; HUMANS; MALE; MELANOMA; OSTEOSARCOMA; PROSTATE; RNA POLYMERASE I; SMALL MOLECULE LIBRARIES;

EID: 84918793897     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-14-0256     Document Type: Article

References (38)

1. Wiman KG. Restoration of wild-type p53 function in human tumors: strategies for efficient cancer therapy. Adv Cancer Res 2007;97:321-38.
2. Brown CJ, Lain S, Verma CS, Fersht AR, Lane DP. Awakening guardian angels: drugging the p53 pathway. Nat Rev Cancer 2009;9:862-73.
3. Wiman KG. Pharmacological reactivation of mutant p53: from protein structure to the cancer patient. Oncogene 2010;29:4245-52.
4. Lehmann S, Bykov VJ, Ali D, Andren O, Cherif H, Tidefelt U, et al. Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. J Clin Oncol 2012;30:3633-9.
5. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004;303:844-8.
6. Tovar C, Graves B, Packman K, Filipovic Z, Higgins B, Xia M, et al. MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models. Cancer Res 2013;73:2587-97.
7. Zhao Y, Bernard D, Wang S. Small molecule inhibitors of MDM2-p53 and MDMX-p53 interactions as new cancer therapeutics. Bio Discov 2013;8:4.
8. Peltonen K, Colis L, Liu H, Jaaämaa S, Moore HM, Enback J, et al. Identification of novel p53 pathway activating small-molecule compounds reveals unexpected similarities with known therapeutic agents. PLoS ONE 2010;5:e12996.
9. Peltonen K, Colis L, Liu H, Trivedi R, Moubarek MS, Moore HM, et al. A targeting modality for destruction of RNA polymerase I that possesses anticancer activity. Cancer Cell 2014;25:77-90.
10. Grummt I. Wisely chosen paths-regulation of rRNA synthesis. FEBS J 2010;277:4626-39.
11. Drygin D, Rice WG, Grummt I. The RNA polymerase I transcription machinery: an emerging target for the treatment of cancer. Annu Rev Pharmacol Toxicol 2010;50:131-56.
12. Bywater MJ, Pearson RB, McArthur GA, Hannan RD. Dysregulation of the basal RNA polymerase transcription apparatus in cancer. Nat Rev Cancer 2013;13:299-314.
13. Russell J, Zomerdijk JC. The RNA polymerase I transcription machinery. Biochem Soc Symp 2006;73:203-16.
14. Gorski SA, Snyder SK, John S, Grummt I, Misteli T. Modulation of RNA polymerase assembly dynamics in transcriptional regulation. Mol Cell 2008;30:486-97.
15. Stefanovsky V, Langlois F, Gagnon-Kugler T, Rothblum LI, Moss T. Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling. Mol Cell 2006;21:629-39.
16. McStay B, Grummt I. The epigenetics of rRNA genes: from molecularto chromosome biology. Annu Rev Cell Dev Biol 2008;24:131-57.
17. Pederson T. The nucleolus. Cold Spring Harb Perspect Biol 2011;3:pii: a000638.
18. Hernandez-Verdun D, Roussel P, Thiry M, Sirri V, Lafontaine DL. The nucleolus: structure/function relationship in RNA metabolism. Wiley Interdiscip Rev RNA 2010;1:415-31.
19. Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, et al. Nucleolar proteome dynamics. Nature 2005;433:77-83.
20. Boulon S, Westman BJ, Hutten S, Boisvert FM, Lamond AI. The nucleolus under stress. Mol Cell 2010;40:216-27.
21. Moore HM, Bai B, Boisvert FM, Latonen L, Rantanen V, Simpson JC, et al. Quantitative proteomics and dynamic imaging of the nucleolus reveal distinct responses to UV and ionizing radiation. Mol Cell Proteomics 2011;10:M111.009241.
22. Shav-Tal Y, Blechman J, Darzacq X, Montagna C, Dye BT, Patton JG, et al. Dynamic sorting of nuclear components into distinct nucleolar caps during transcriptional inhibition. Mol Biol Cell 2005;16:2395-413.
23. Rubbi CP, Milner J. Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses. EMBO J 2003; 22:6068-77.
24. Kurki S, Peltonen K, Latonen L, Kiviharju TM, Ojala PM, Meek D, et al. Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation. Cancer Cell 2004;5:465-75.
25. Zhang Y, Lu H. Signaling to p53: ribosomal proteins find their way. Cancer Cell 2009;16:369-77.
26. Bursac S, Donati G, Brdovcak MC, Volarevic S. Activation of the tumor suppressor p53 upon impairment of ribosome biogenesis. Biochim Biophys Acta 2013;pii:S0925-4439(13)00306-2.
27. Grisendi S, Mecucci C, Falini B, Pandolfi PP. Nucleophosmin and cancer. Nat Rev Cancer 2006;6:493-505.
28. Montanaro L, Trere D, Derenzini M. Nucleolus, ribosomes, and cancer. Am J Pathol 2008;173:301-10.
29. Moore HM, Bai B, Matilainen O, Colis L, Peltonen K, Laiho M. Proteasome activity influences UV-mediated subnuclear localization changes of NPM. PLoS One 2013;8:e59096.
30. Jaaämaa S, Af Hallstrom TM, Sankila A, Rantanen V, Koistinen H, Stenman UH, et al. DNA damage recognition via activated ATM and p53 pathway in nonproliferating human prostate tissue. Cancer Res 2010;70:8630-41.
31. Zhang Z, Yang Z, Jaamaa S, Liu H, Pellakuru LG, Iwata T, et al. Differential epithelium DNA damage response to ATM and DNA-PK pathway inhibition in human prostate tissue culture. Cell Cycle 2011; 10:3545-53.
32. Shoemaker RH. The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer 2006;6:813-23.
33. Budde A, Grummt I. p53 represses ribosomal gene transcription. Oncogene 1999;18:1119-24.
34. Zhai W, Comai L. Repression of RNA polymerase I transcription by the tumor suppressor p53. Mol Cell Biol 2000;20:5930-8.
35. Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res 2010;70:440-6.
36. Bywater MJ, Poortinga G, Sanij E, Hein N, Peck A, Cullinane C, et al. Inhibition of RNA polymerase I as a therapeutic strategy to promote cancer-specific activation of p53. Cancer Cell 2012;22:51-65.
37. Drygin D, Lin A, Bliesath J, Ho CB, O'Brien SE, Proffitt C, et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res 2011; 71:1418-30.
38. Burger K, Muhl B, Harasim T, Rohrmoser M, Malamoussi A, Orban M, et al. Chemotherapeutic drugs inhibit ribosome biogenesis at various levels. J Biol Chem 2010;285:12416-25.