A Small Molecule Inhibits Deregulated NRF2 Transcriptional Activity in Cancer

ACS Chemical Biology

Volumn 10, Issue 10, 2015, Pages 2193-2198

  Bollong, Michael J ^a   Yun, Hwayoung ^a   Sherwood, Lance ^b   Woods, Ashley K ^b   Lairson, Luke L ^a,b   Schultz, Peter G ^a,b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b California Institute for Biomedical Research   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AEM1; ANTINEOPLASTIC AGENT; DOXORUBICIN; ETOPOSIDE; FLUOROURACIL; TRANSCRIPTION FACTOR NRF2; UNCLASSIFIED DRUG; 2-AMINO-5-ETHYLIDENE-1-METHYLIMIDAZOL-4-ONE; IMIDAZOLE DERIVATIVE; MOLECULAR LIBRARY;

A549 CELL LINE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER INHIBITION; DRUG MECHANISM; DRUG STRUCTURE; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LUNG CANCER; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL LINE; CELL SURVIVAL; CHEMISTRY; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; MOLECULAR LIBRARY; NEOPLASM; NUDE MOUSE; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PHARMACOLOGY; PRECLINICAL STUDY; TUMOR CELL LINE;

ANIMALS; CELL LINE; CELL LINE, TUMOR; CELL SURVIVAL; DRUG EVALUATION, PRECLINICAL; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMIDAZOLES; MALE; MICE; MICE, NUDE; NEOPLASMS; NF-E2-RELATED FACTOR 2; OXIDATIVE STRESS; SMALL MOLECULE LIBRARIES;

EID: 84944730962     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/acschembio.5b00448     Document Type: Article

References (17)

1. Kensler, T. W., Wakabayashi, N., and Biswal, S. (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway Annu. Rev. Pharmacol. Toxicol. 47, 89-116 10.1146/annurev.pharmtox.46.120604.141046
2. English, C. and Aloi, J. J. (2015) New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis Clin. Ther. 37, 691-715 10.1016/j.clinthera.2015.03.001
3. Hu, J., Xu, Q., McTiernan, C., Lai, Y. C., Osei-Hwedieh, D., and Gladwin, M. (2015) Novel Targets of Drug Treatment for Pulmonary Hypertension Am. J. Cardiovasc. Drugs 15, 225 10.1007/s40256-015-0125-4
4. Zhang, Y. and Munday, R. (2008) Dithiolethiones for cancer chemoprevention: where do we stand? Mol. Cancer Ther. 7, 3470-3479 10.1158/1535-7163.MCT-08-0625
5. Arlt, A., Sebens, S., Krebs, S., Geismann, C., Grossmann, M., Kruse, M. L., Schreiber, S., and Schafer, H. (2013) Inhibition of the Nrf2 transcription factor by the alkaloid trigonelline renders pancreatic cancer cells more susceptible to apoptosis through decreased proteasomal gene expression and proteasome activity Oncogene 32, 4825-4835 10.1038/onc.2012.493
6. Leinonen, H. M., Kansanen, E., Polonen, P., Heinaniemi, M., and Levonen, A. L. (2014) Role of the Keap1-Nrf2 pathway in cancer Adv. Cancer Res. 122, 281-320 10.1016/B978-0-12-420117-0.00008-6
7. Kim, T. H., Hur, E. G., Kang, S. J., Kim, J. A., Thapa, D., Lee, Y. M., Ku, S. K., Jung, Y., and Kwak, M. K. (2011) NRF2 blockade suppresses colon tumor angiogenesis by inhibiting hypoxia-induced activation of HIF-1alpha Cancer Res. 71, 2260-2275 10.1158/0008-5472.CAN-10-3007
8. Abazeed, M. E., Adams, D. J., Hurov, K. E., Tamayo, P., Creighton, C. J., Sonkin, D., Giacomelli, A. O., Du, C., Fries, D. F., Wong, K. K., Mesirov, J. P., Loeffler, J. S., Schreiber, S. L., Hammerman, P. S., and Meyerson, M. (2013) Integrative radiogenomic profiling of squamous cell lung cancer Cancer Res. 73, 6289-6298 10.1158/0008-5472.CAN-13-1616
9. DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., Scrimieri, F., Winter, J. M., Hruban, R. H., Iacobuzio-Donahue, C., Kern, S. E., Blair, I. A., and Tuveson, D. A. (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis Nature 475, 106-109 10.1038/nature10189
10. Singh, A., Boldin-Adamsky, S., Thimmulappa, R. K., Rath, S. K., Ashush, H., Coulter, J., Blackford, A., Goodman, S. N., Bunz, F., Watson, W. H., Gabrielson, E., Feinstein, E., and Biswal, S. (2008) RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy Cancer Res. 68, 7975-7984 10.1158/0008-5472.CAN-08-1401
11. Hur, W. and Gray, N. S. (2011) Small molecule modulators of antioxidant response pathway Curr. Opin. Chem. Biol. 15, 162-173 10.1016/j.cbpa.2010.12.009
12. Ki, S. H., Cho, I. J., Choi, D. W., and Kim, S. G. (2005) Glucocorticoid receptor (GR)-associated SMRT binding to C/EBPbeta TAD and Nrf2 Neh4/5: role of SMRT recruited to GR in GSTA2 gene repression Mol. Cell. Biol. 25, 4150-4165 10.1128/MCB.25.10.4150-4165.2005
13. Singh, A., Misra, V., Thimmulappa, R. K., Lee, H., Ames, S., Hoque, M. O., Herman, J. G., Baylin, S. B., Sidransky, D., Gabrielson, E., Brock, M. V., and Biswal, S. (2006) Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer PLoS Med. 3, e420 10.1371/journal.pmed.0030420
14. Malhotra, D., Portales-Casamar, E., Singh, A., Srivastava, S., Arenillas, D., Happel, C., Shyr, C., Wakabayashi, N., Kensler, T. W., Wasserman, W. W., and Biswal, S. (2010) Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis Nucleic Acids Res. 38, 5718-5734 10.1093/nar/gkq212
15. Mitsuishi, Y., Taguchi, K., Kawatani, Y., Shibata, T., Nukiwa, T., Aburatani, H., Yamamoto, M., and Motohashi, H. (2012) Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming Cancer Cell 22, 66-79 10.1016/j.ccr.2012.05.016
16. Ren, D., Villeneuve, N. F., Jiang, T., Wu, T., Lau, A., Toppin, H. A., and Zhang, D. D. (2011) Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism Proc. Natl. Acad. Sci. U. S. A. 108, 1433-1438 10.1073/pnas.1014275108
17. Bryan, H. K., Olayanju, A., Goldring, C. E., and Park, B. K. (2013) The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation Biochem. Pharmacol. 85, 705-717 10.1016/j.bcp.2012.11.016