Potent targeting of the STAT3 protein in brain cancer stem cells: A promising route for treating glioblastoma

ACS Medicinal Chemistry Letters

Volumn 4, Issue 11, 2013, Pages 1102-1107

  Haftchenary, Sina ^a   Luchman, H Artee ^b   Jouk, Andriana O ^a   Veloso, Anthony J ^a   Page, Brent D G ^a   Cheng, Xin Ran ^a   Dawson, Sean S ^a   Grinshtein, Natalie ^c   Shahani, Vijay M ^a   Kerman, Kagan ^a   Kaplan, David R ^c   Griffin, Carly ^d   Aman, Ahmed M ^d   Al Awar, Rima ^d   Weiss, Samuel ^b   Gunning, Patrick T ^a  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF CALGARY   (Canada)

^c HOSPITAL FOR SICK CHILDREN   (Canada)

^d ONTARIO INSTITUTE FOR CANCER RESEARCH   (Canada)

Author keywords

anticancer drug; brain cancer stem cells; glioblastoma; protein protein interactions; small molecule inhibitor; STAT3

Indexed keywords

ANTINEOPLASTIC AGENT; BP 1 102; PROTEIN INHIBITOR OF ACTIVATED STAT; SH 4 54; STAT3 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; ARTICLE; ASTROCYTE; BLOOD BRAIN BARRIER; BRAIN CANCER; CANCER STEM CELL; CELL KILLING; CYTOTOXICITY; DRUG EFFICACY; DRUG PROTEIN BINDING; DRUG TARGETING; ENZYME INHIBITION; GLIOBLASTOMA; IMMUNOHISTOCHEMISTRY; MAXIMUM TOLERATED DOSE; MOUSE; NOD SCID MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; TUMOR GROWTH;

EID: 84887860405     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml4003138     Document Type: Article

References (27)

1. Stupp, T.; Mason, W. P.; Van den Bent, M. J.; Weller, M.; Fisher, B.; Taphoorn, M. J.; Belanger, K.; Brandes, A. A.; Marosi, C.; Bogdahn, U.; Curschmann, J.; Janzer, R. C.; Ludwin, S. K.; Gorlia, T.; Allgeier, A. L.; Lacombe, D.; Cairncross, J. G.; Eisenhauer, E.; Mirimanoff, R. O. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma New Engl. J. Med. 2005, 352, 987-96
2. Yuan, S. H.; Martin, J.; Elia, J.; Flippin, J.; Paramban, R. I.; Hefferan, M. P.; Vidal, J. G.; Mu, Y.; Killian, R. L.; Israel, M. A.; Emre, N.; Marsala, S.; Marsala, M.; Gage, F. H.; Goldstein, L. S.; Carson, C. T. Cell-surface marker signatures for the isolation of neural stem cells, glia and neurons derived from human pluripotent stem cells PLoS One 2011, 6, e17540
3. Bleau, A. M.; Hambardzumyan, D.; Ozawa, T.; Fomchenko, E. I.; Huse, J. T.; Brennan, C. W.; Holland, E. C. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells Cell Stem Cell 2009, 3, 226-35
4. Salmaggi, A.; Boiardi, A.; Gelati, M.; Russo, A.; Calatozzolo, C.; Ciusani, E.; Sciacca, F. L.; Ottolina, A.; Parati, E. A.; La Porta, C.; Alessandri, G.; Marras, C.; Croci, D.; De Rossi, M. Glioblastoma-derived tumorospheres identify a population of tumor stem-like cells with angiogenic potential and enhanced multidrug resistance phenotype Glia 2006, 54, 850-860
5. Carro, M. S.; Lim, W. K.; Alvarez, M. J.; Bollo, R. J.; Zhao, X.; Snyder, E. Y.; Sulman, E. P.; Anne, S. L.; Doetsch, F.; Colman, H.; Lasorella, A.; Aldape, K.; Califano, A.; Iavarone, A. The transcriptional network for mesenchymal transformation of brain tumours Nature 2010, 463, 318-325
6. Stechishin, O. D.; Luchman, H. A.; Ruan, Y.; Blough, M. D.; Nguyen, S. A.; Kelly, J. J.; Cairncross, J. G.; Weiss, S. On-target JAK2/STAT3 inhibition slows disease progression in orthotopic xenografts of human glioblastoma brain tumor stem cells Neuro-Oncology 2013, 15, 198-207
7. Villalva, C.; Martin-Lannerée, S.; Cortes, U.; Dkhissi, F.; Wager, M.; Le Corf, A.; Tourani, J. M.; Dusanter-Fourt, I.; Turhan, A. G.; Karayan-Tapon, L. STAT3 is essential for the maintenance of neurosphere- initiating tumor cells in patients with glioblastomas: A potential for targeted therapy? Int. J. Cancer 2011, 128, 826-838
8. Haftchenary, S.; Avadisian, M.; Gunning, P. T. Towards the development of small molecule inhibitors of Stat3 dimerization Anti-Cancer Drugs 2011, 22, 115-127
9. Leong, P. L.; Andrews, G. A.; Johnson, D. E.; Dyer, K. F.; Sichuan, X.; Jeffrey, C. M.; Robbins, P. D.; Gadiparthi, S.; Burke, N. A.; Watkins, S. F.; Grandis, J. R. Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth Proc. Natl. Acad. Sci. U.S.A. 2003, 7, 4138-4143
10. Chen, X.; Vinkemeier, U.; Zhao, Y.; Jeruzalmi, D.; Darnell, J. E.; Kuriyan, J. Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA Cell 1998, 93, 827-839
11. Xi, S.; Gooding, W. E.; Grandis, J. R. In vivo antitumor efficacy of STAT3 blockade using a transcription factor decoy approach: Implications for cancer therapy Oncogene 2005, 24, 970-979
12. Stahl, N.; Farruggella, T. J.; Boulton, T. G.; Zhong, Z.; Darnell, J. E.; Yancopoulos, G. D. Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors Science 1995, 267, 1349-1353
13. Shahani, V. M.; Yue, P.; Fletcher, S.; Sharmeen, S.; Sukhai, M. A.; Luu, D. P.; Zhang, X.; Sun, H.; Zhao, W.; Schimmer, A. D.; Turkson, J.; Gunning, P. T. Design, Synthesis and in vitro characterization of novel hybrid peptidomimetic inhibitors of STAT3 protein Bioorg. Med. Chem. 2011, 19, 1823-1838
14. Chen, J.; Bai, L.; Bernard, D.; Nikolovska-Coleska, Z.; Gomez, C.; Zhang, J.; Yi, H.; Wang, S. Structure-based design of conformationally constrained, cell-permeable STAT3 inhibitors ACS Med. Chem. Lett. 2010, 1, 85-89
15. Mao, X.; Ren, Z.; Parker, G. N.; Sondermann, H.; Pastorello, M. A.; Wang, W.; McMurray, J. S.; Demeler, B.; Darnell, J. E., Jr.; Chen, X. Structural bases of unphosphorylated STAT1 association and receptor binding Mol. Cell 2005, 17, 761-771
16. Fletcher, S.; Singh, J.; Zhang, X.; Yue, P.; Page, B. D. G.; Sharmeen, S.; Shahani, V. M.; Zhao, W.; Schimmer, A. D.; Turkson, J.; Gunning, P. T. Disruption of transcriptionally active Stat3 dimers with non-phosphorylated, salicylic acid-based small molecules: Potent in vitro and tumor cell activities ChemBioChem 2009, 10, 1959-1964
17. Page, B. D. G.; Fletcher, S.; Yue, P.; Li, Z.; Zhang, X.; Sharmeen, S.; Datti, A.; Wrana, J. L.; Trudel, S.; Schimmer, A. D.; Turkson, J.; Gunning, P. T. Identification of a nonphosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain Bioorg. Med. Chem. 2011, 21, 5605-5609
18. Fletcher, S.; Page, B. D. G.; Zhang, X.; Yue, P.; Li, Z. H.; Sharmeen, S.; Singh, J.; Zhao, W.; Schimmer, A. D.; Trudel, S.; Turkson, J.; Gunning, P. T. Antagonism of the Stat3-Stat3 protein dimer with salicylic acid-based small molecules ChemMedChem 2011, 6, 1459-1470
19. Zhang, X.; Yue, P.; Page, B. D. G.; Lia, T.; Zhao, W.; Namanja, A. T.; Paladino, D.; Zhaoa, J.; Chen, Y.; Gunning, P. T.; Turkson, J. An orally-bioavailable small-molecule Stat3 inhibitor regresses human breast and lung cancer xenografts Proc. Natl. Acad. Sci. 2012, 33, 2450-2456
20. Page, B. D. G.; Khoury, H.; Laister, R. C.; Fletcher, S.; Vellozo, M.; Manzoli, A.; Yue, P.; Turkson, J.; Minden, M. D.; Gunning, P. T. Small molecule STAT5-SH2 domain inhibitors exhibit potent anti-leukemia activity J. Med. Chem. 2012, 55, 1046-1055
21. Kelly, J. J.; Stechishin, O.; Chojnacki, A.; Lun, X.; Sun, B.; Senger, D. L.; Forsyth, P.; Auer, R. N.; Dunn, J. F.; Cairncross, J. G.; Parney, I. F.; Weiss, S. Proliferation of human glioblastoma stem cells occurs independently of exogenous mitogens Stem Cells 2009, 27, 1722-1733
22. Coleman, D. R.; Ren, Z.; Mandal, P. K.; Cameron, A. G.; Dyer, G. A.; Muranjan, S.; Campbell, M.; Chen, X.; McMurray, J. S. Investigation of the binding determinants of phosphopeptides targeted to the SRC homology 2 domain of the signal transducer and activator of transcription 3. Development of a high-affinity peptide inhibitor J. Med. Chem. 2005, 48, 6661-6670
23. Schust, J.; Berg, T. A high-throughput fluorescence polarization assay for STAT3 Anal. Biochem. 2004, 330, 114-118
24. Wu, P.; Brasseur, M.; Schindler, U. A high-throughput STAT binding assay using fluorescence polarization Anal. Biochem. 1997, 249, 29-36
25. Verkaar, F.; Van Rosmalen, J. W.; Blomenröhr, M.; Van Koppen, C. J.; Blankesteijn, W. M.; Smits, J. F.; Zaman, G. J. G protein-independent cell-based assays for drug discovery on seven-transmembrane receptors Biotechnol. Annu. Rev. 2008, 14, 253-274
26. McFarland, B. C.; Ma, J. Y.; Langford, C. P.; Gillespie, G. Y.; Yu, H.; Zheng, Y.; Nozell, S. E.; Huszar, D.; Benveniste, E. N. Therapeutic potential of AZD1480 for the treatment of human glioblastoma Mol. Cancer Ther. 2011, 12, 2384-2393
27. Tefferi, A. JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths Blood 2012, 119, 2721-27