Novel small molecule, XZH-5, inhibits constitutive and interleukin-6-induced STAT3 phosphorylation in human rhabdomyosarcoma cells

Cancer Science

Volumn 102, Issue 7, 2011, Pages 1381-1387

  Liu, Aiguo ^a,b,c   Liu, Yan ^a,b,e   Xu, Zhenghu ^d   Yu, Wenying ^b   Wang, Hong ^d   Li, Chenglong ^b   Lin, Jiayuh ^a,b  

^a THE RESEARCH INSTITUTE AT NATIONWIDE CHILDREN S HOSPITAL   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^d MIAMI UNIVERSITY   (United States)

^e VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CYCLIN D1; GAMMA INTERFERON; INTERLEUKIN 6; PEPTIDOMIMETIC AGENT; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN INHIBITOR; STAT1 PROTEIN; STAT3 PROTEIN; SURVIVIN; TYROSINE; UNCLASSIFIED DRUG; XZH 5;

APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL MIGRATION; CELL VIABILITY; COLONY FORMING UNIT; CONTROLLED STUDY; DNA BINDING; DOWN REGULATION; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG STRUCTURE; HUMAN; HUMAN TISSUE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RHABDOMYOSARCOMA; SIGNAL TRANSDUCTION;

ACTIVE TRANSPORT, CELL NUCLEUS; APOPTOSIS; CELL LINE, TUMOR; CELL MOVEMENT; DRUG DISCOVERY; HISTIDINE; HUMANS; INTERLEUKIN-6; PHENYLUREA COMPOUNDS; PHOSPHORYLATION; RHABDOMYOSARCOMA; STAT3 TRANSCRIPTION FACTOR; WOUND HEALING;

EID: 79959269602     PISSN: 13479032     EISSN: 13497006     Source Type: Journal    
DOI: 10.1111/j.1349-7006.2011.01932.x     Document Type: Article

References (40)

1. Darnell JJ, Kerr I, Stark G. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994; 264: 1415-21.
2. Zhong Z, Wen Z, Darnell JJ. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 1994; 264: 95-8.
3. Bromberg JF, Wrzeszcznska MH, Devgan G et al. STAT 3 as an oncogene. Cell 1999; 98: 295-303.
4. Inghirami G, Chiarle R, Simmons WJ, Piva R, Schlessinger K, Levy DE. New and old functions of STAT3: a pivotal target for individualized treatment of cancer. Cell Cycle 2005; 4: 1131-3.
5. Schlessinger K, Levy DE. Malignant transformation but not normal cell growth depends on signal transducer and activator of transcription 3. Cancer Res 2005; 65: 5828-34.
6. 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: 7611-8.
7. Shen Y, Devgan G, Darnell JJ, Bromberg J. Constitutively activated Stat3 protects fibroblasts from serum withdrawal and UV-induced apoptosis and antagonizes the proapoptotic effects of activated Stat1. Proc Natl Acad Sci USA 2001; 98: 1543-8.
8. 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; 10: 48-54.
9. Buettner R, Mora L, Jove R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 2002; 8: 945-54.
10. Alas S, Bonavida B. Inhibition of constitutive stat3 activity sensitizes resistant non-hodgkin's lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis. Clin Cancer Res 2003; 9: 316-26.
11. Aoki Y, Feldman G, Tosato G. Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood 2003; 101: 1535-42.
12. Ling X, Arlinghaus RB. Knockdown of STAT3 expression by RNA interference inhibits the induction of breast tumors in immunocompetent mice. Cancer Res 2005; 65: 2532-6.
13. Kaptein A, Paillard V, Saunders M. Dominant negative stat3 mutant inhibits interleukin-6-induced Jak-STAT signal transduction. J Biol Chem 1996; 271: 5961-4.
14. 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.
15. 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 USA 2005; 102: 4700-5.
16. Niu G, Heller R, Catlett-Falcone R et al. Gene therapy with dominant-negative STAT 3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res 1999; 59: 5059-63.
17. 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: 7925-34.
18. Catlett-Falcone R, Landowski TH, Oshiro MM et al. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 1999; 10: 105-15.
19. Bowman T, Broome MA, Sinibaldi D et al. Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci USA 2001; 98: 7319-24.
20. Chen CL, Loy A, Cen L et al. Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells. BMC cancer 2007; 7: 111.
21. McMurray JS. A new small-molecule Stat3 inhibitor. Chem Biol 2006; 13: 1123-4.
22. Sansone P, Storci G, Tavolari S et al. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 2007; 117: 3988-4002.
23. Schafer ZT, Brugge JS. IL-6 involvement in epithelial cancers. J Clin Invest 2007; 117: 3660-3.
24. Grivennikov S, Karin M. Autocrine IL-6 signaling: a key event in tumorigenesis? Cancer Cell 2008; 13: 7-9.
25. Tang Y, Kitisin K, Jogunoori W et al. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci USA 2008; 105: 2445-50.
26. Dauer DJ, Ferraro B, Song L, et al. Stat3 regulates genes common to both wound healing and cancer. Oncogene 2005; 24: 3397-408.
27. Abdulghani J, Gu L, Dagvadorj A et al. Stat3 promotes metastatic progression of prostate cancer. Am J Pathol 2008; 172: 1717-28.
28. Crist W, Gehan EA, Ragab AH et al. The third intergroup rhabdomyosarcoma study. J Clin Oncol 1995; 13: 610-30.
29. Koscielniak E, Morgan M, Treuner J. Soft tissue sarcoma in children: prognosis and management. Paediatr Drugs 2002; 4: 21-8.
30. Bai L, Yu Z, Qian G et al. SOCS3 was induced by hypoxia and suppressed STAT3 phosphorylation in pulmonary arterial smooth muscle cells. Respir Physiol Neurobiol 2006; 152: 83-91.
31. Wei CC, Ball S, Lin L et al. Two small molecule compounds, LLL12 and FLLL32, exhibit potent inhibitory activity on STAT3 in human rhabdomyosarcoma cells. Int J Oncol 2010; 38: 279-85.
32. Hodge DR, Hurt EM, Farrar WL. The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer 2005; 41: 2502-12.
33. Nakagawa H, Maeda S, Yoshida H et al. Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: an analysis based on gender differences. Int J Cancer 2009; 125: 2264-9.
34. Liu Y, Fuchs J, Li C, Lin J. IL-6, a risk factor for hepatocellular carcinoma: FLLL32 inhibits IL-6-induced STAT3 phosphorylation in human hepatocellular cancer cells. Cell Cycle 2010; 9: 3423-7.
35. Knupfer H, Preiss R. Significance of interleukin-6 (IL-6) in breast cancer (review). Breast Cancer Res Treat 2007; 102: 129-35.
36. Cozen W, Gill PS, Ingles SA et al. IL-6 levels and genotype are associated with risk of young adult Hodgkin lymphoma. Blood 2004; 103: 3216-21.
37. Liu Y, Li PK, Li C, Lin J. Inhibition of STAT3 signaling blocks the anti-apoptotic activity of IL-6 in human liver cancer cells. J Biol Chem 2010; 285: 27429-39.
38. Huang C, Yang G, Jiang T, Huang K, Cao J, Qiu Z. Effects of IL-6 and AG490 on regulation of Stat3 signaling pathway and invasion of human pancreatic cancer cells in vitro. J Exp Clin Cancer Res 2010; 29: 51.
39. Ulivi P, Arienti C, Amadori D et al. Role of RAF/MEK/ERK pathway, p-STAT-3 and Mcl-1 in sorafenib activity in human pancreatic cancer cell lines. J Cell Physiol 2009; 220: 214-21.
40. Lin L, Hutzen B, Zuo M et al. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells. Cancer Res 2010; 70: 2445-54.