Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells

Cancer Research

Volumn 70, Issue 6, 2010, Pages 2445-2454

  Lin, Li ^a,c   Hutzen, Brian ^a,b   Zuo, Mingxin ^a   Ball, Sarah ^a,b   Deangelis, Stephanie ^a   Foust, Elizabeth ^a   Pandit, Bulbul ^b   Ihnat, Michael A ^d   Shenoy, Satyendra S ^d   Kulp, Samuel ^b   Li, Pui Kai ^b   Li, Chenglong ^b   Fuchs, James ^b   Lin, Jiayuh ^a,b  

^a THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^d UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; CURCUMIN; DNA; DOXORUBICIN; FLLL31; FLLL32; INTERLEUKIN 6; JANUS KINASE 2; PROTEIN TYROSINE PHOSPHATASE SHP; STAT3 PROTEIN; TURMERIC; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER INHIBITION; CELL INVASION; COLONY FORMATION; CONTROLLED STUDY; DIMERIZATION; DNA BINDING; DRUG EFFICACY; EMBRYO; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; MOUSE; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TUMOR VOLUME;

ANIMALS; BREAST NEOPLASMS; CELL GROWTH PROCESSES; CELL LINE, TUMOR; CHICK EMBRYO; CURCUMIN; DOWN-REGULATION; FEMALE; HUMANS; JANUS KINASE 2; MICE; MICE, NUDE; MODELS, MOLECULAR; PANCREATIC NEOPLASMS; PHOSPHORYLATION; SRC HOMOLOGY DOMAINS; STAT3 TRANSCRIPTION FACTOR; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77950190311     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-09-2468     Document Type: Article

References (44)

1. Zhong Z, Wen Z, Darnell J. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 1994;264:95-98
2. Sasse J, Hemmann U, Schwartz C, et al. Mutational analysis of acute-phase response factor/Stat3 activation and dimerization. Mol Cell Biol 1997;17:4677-4686
3. Yu H, Jove R. The STATs of cancer - new molecular targets come of age. Nat Rev Cancer 2004;4:97-105.
4. Buettner R, Mora LB, Jove R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 2002;8:945-954
5. Real P, Sierra A, De Juan A, Segovia J, Lopez-Vega J, Fernandez-Luna J. Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells. Oncogene 2002;21:7611-7618
6. Wang T, Niu G, Kortylewski M, et al. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med 2004:48-54.
7. Aoki Y, Feldman G, Tosato G. Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood 2003;101:1535-1542
8. Burke W, Jin X, Liu R, Huang M, Reynolds RK, Lin J. Inhibition of constitutively active Stat3 pathway in ovarian and breast cancer cells. Oncogene 2001;20:7925-7934
9. Calvin D, Nam S, Buettner R, Sekharam M, Torres-Roca J, Jove R. Inhibition of STAT3 activity with STAT3 antisense oligonucleotide (STAT3-ASO) enhances radiation-induced apoptosis in DU145 prostate cancer cells. Int J Radiat Oncol Biol Phys 2003;57:S297.
10. Kaptein A, Paillard V, Saunders M. Dominant negative stat3 mutant inhibits interleukin-6-induced Jak-STAT signal transduction. J Biol Chem 1996;271:5961-5964
11. Takeda K, Noguchi K, Shi W, et al. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci U S A 1997;94:3801-3804
12. Akira S. Roles of STAT3 defined by tissue-specific gene targeting. Oncogene 2000;19:2607-2611
13. Aggarwal BB, Sethi G, Ahn KS, et al. Targeting signal-transducer-and- activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann N Y Acad Sci 2006;1091:151-169
14. Duan Z, Bradner JE, Greenberg E, et al. SD-1029 inhibits signal transducer and activator of transcription 3 nuclear translocation. Clin Cancer Res 2006;12:6844-6852
15. Meydan N, Grunberger T, Dadi H, et al. Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor. Nature 1996;379:645-648
16. Iwamaru A, Szymanski S, Iwado E, et al. A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both in vitro and in vivo. Oncogene 2007;26:2435-2444
17. Song H, Wang R, Wang S, Lin J. A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells. Proc Natl Acad Sci U S A 2005;102:4700-4705
18. Turkson J, Ryan D, Kim J, et al. Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation. J Biol Chem 2001;276:45443-45455
19. Coleman DRt, Ren Z, Mandal PK, et al. 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
20. Schust J, Sperl B, Hollis A, Mayer TU, Berg T. Stattic: a small-molecule inhibitor of STAT3 activation and dimerization. Chem Biol 2006;13:1235-1242
21. Siddiquee K, Zhang S, Guida WC, et al. Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proc Natl Acad Sci U S A 2007;104:7391-7396
22. Hatcher H, Planalp R, Cho J, TortiFM, Torti SV. Curcumin: fromancient medicine to current clinical trials. Cell Mol Life Sci 2008;65:1631-1652
23. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": from kitchen to clinic. Biochem Pharmacol 2008;75:787-809.
24. Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci 2009;30:85-94.
25. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm 2007;4:807-818
26. Turkson J, Bowman T, Garcia R, Caldenhoven E, De Groot RP, Jove R. Stat3 activation by src induces specific gene regulation and is required for cell transformation. Mol Cell Biol 1998;18:2545-2552
27. Bromberg J, Wrzeszczynska M, Devgan G, et al. Stat3 as an oncogene. Cell 1999;98:295-303.
28. Lucarelli E, Sangiorgi L, Benassi S, et al. Angiogenesis in lipoma: an experimental study in the chick embryo chorioallantoic membrane. Int J Mol Med 1999;4:593-596
29. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.
30. Lin L, Shi Q, Nyarko AK, et al. Antitumor agents. 250. Design and synthesis of new curcumin analogues as potential anti-prostate cancer agents. J Med Chem 2006;49:3963-3972
31. Amolins MW, Peterson LB, Blagg BS. Synthesis and evaluation of electron-rich curcumin analogues. Bioorg Med Chem Lett 2009;17:360-367
32. Levy DE, Darnell JE, Jr. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 2002;3:651-662
33. Reich NC, Liu L. Tracking STAT nuclear traffic. Nat Rev 2006;6:602-612
34. Frank DA. STAT3 as a central mediator of neoplastic cellular transformation. Cancer Lett 2007;251:199-210.
35. Kanda N, Seno H, Konda Y, et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene 2004;23:4921-4929
36. Bromberg J, Horvath C, Wen Z, Schreiber R, Darnell JJ. Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon α and interferon γ. Proc Natl Acad Sci U S A 1996;93:7673-7678
37. Stephanou A, Latchman DS. STAT-1: a novel regulator of apoptosis. Int J Exp Pathol 2003;84:239-244
38. Wylie PG, Bowen WP. Determination of cell colony formation in a high-content screening assay. Clin Lab Med 2007;27:193-199
39. Kang Y, Siegel PM, Shu W, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003;3:537-549
40. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin 2008;58:71-96.
41. Darnell JE, Jr. Transcription factors as targets for cancer therapy. Nat Rev Cancer 2002;2:740-749
42. Chakravarti N, Myers J, Aggarwal B. Targeting constitutive and interleukin-6-inducible signal transducers and activators of transcription 3 pathway in head and neck squamous cell carcinoma cells by curcumin (diferuloylmethane). Int J Cancer 2006;119:1268-1275
43. Bharti A, Donato N, Aggarwal B. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol 2003;171:3863-3871
44. Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Adv Exp Med Biol 2007;595:1-75.