Targeting transcription factor STAT3 for cancer prevention and therapy

Pharmacology and Therapeutics

Volumn 162, Issue , 2016, Pages 86-97

  Chai, Edna Zhi Pei ^a   Shanmugam, Muthu K ^a   Arfuso, Frank ^b   Dharmarajan, Arunasalam ^b   Wang, Chao ^a,c   Kumar, Alan Prem ^a,b,c,d   Samy, Ramar Perumal ^e   Lim, Lina H K ^e   Wang, Lingzhi ^a,c   Goh, Boon Cher ^a,c,f   Ahn, Kwang Seok ^g   Hui, Kam Man ^h   Sethi, Gautam ^a,b  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b CURTIN UNIVERSITY   (Australia)

^c NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^d UNIVERSITY OF NORTH TEXAS   (United States)

^e NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^f NATIONAL UNIVERSITY HEALTH SYSTEM   (Singapore)

^g Kyung Hee University   (South Korea)

^h DIVISION OF MEDICAL ONCOLOGY   (Singapore)

Author keywords

Angiogenesis; Apoptosis; Cancer; Cytokines; Proliferation; STAT3

Indexed keywords

5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; ALPHA TOCOPHEROL; BARICITINIB; BOSUTINIB; BUTEIN; CAPSAICIN; CELASTROL; DASATINIB; DIOSGENIN; KARYOPHERIN; LESTAURTINIB; MOMELOTINIB; RESVERATROL; STAT3 PROTEIN; THYMOQUINONE; ANTINEOPLASTIC AGENT;

AMINO TERMINAL SEQUENCE; ARTICLE; CANCER PREVENTION; CARCINOGENESIS; DNA BINDING; ENZYME ACTIVITY; HUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TARGETING; SIGNAL TRANSDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; METABOLISM; NEOPLASMS;

ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOGENESIS; HUMANS; NEOPLASMS; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR;

EID: 84957612113     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2015.10.004     Document Type: Review

References (167)

1. B.B. Aggarwal, G. Sethi, K.S. Ahn, S.K. Sandur, M.K. Pandey, A.B. Kunnumakkara, B. Sung, and H. Ichikawa Targeting signal-transducer-And-Activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution Ann N Y Acad Sci 1091 2006 151 169
2. K.S. Ahn, G. Sethi, K. Krishnan, and B.B. Aggarwal Gamma-tocotrienol inhibits nuclear factor-kappaB signaling pathway through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and potentiation of apoptosis J Biol Chem 282 2007 809 820
3. S. Aittomaki, and M. Pesu Therapeutic targeting of the Jak/STAT pathway Basic Clin Pharmacol Toxicol 114 2014 18 23
4. M. Alkhalaf, A. El-Mowafy, W. Renno, O. Rachid, A. Ali, and R. Al-Attyiah Resveratrol-induced apoptosis in human breast cancer cells is mediated primarily through the caspase-3-dependent pathway Arch Med Res 39 2008 162 168
5. S. Becker, B. Groner, and C.W. Muller Three-dimensional structure of the Stat3beta homodimer bound to DNA Nature 394 1998 145 151
6. J.C. Bendell, D.S. Hong, H.A. Burris III, A. Naing, S.F. Jones, G. Falchook, P. Bricmont, A. Elekes, E.P. Rock, and R. Kurzrock Phase 1, open-label, dose-escalation, and pharmacokinetic study of STAT3 inhibitor OPB-31121 in subjects with advanced solid tumors Cancer Chemother Pharmacol 74 2014 125 130
7. A. Bhardwaj, G. Sethi, S. Vadhan-Raj, C. Bueso-Ramos, Y. Takada, U. Gaur, A.S. Nair, S. Shishodia, and B.B. Aggarwal Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells Blood 109 2007 2293 2302
8. M. Bhutani, A.K. Pathak, A.S. Nair, A.B. Kunnumakkara, S. Guha, G. Sethi, and B.B. Aggarwal Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation Clin Cancer Res 13 2007 3024 3032
9. M.A. Bill, C. Nicholas, T.A. Mace, J.P. Etter, C. Li, E.B. Schwartz, J.R. Fuchs, G.S. Young, L. Lin, J. Lin, L. He, M. Phelps, P.K. Li, and G.B. Lesinski Structurally modified curcumin analogs inhibit STAT3 phosphorylation and promote apoptosis of human renal cell carcinoma and melanoma cell lines PLoS ONE 7 2012 e40724
10. K. Bley, G. Boorman, B. Mohammad, D. McKenzie, and S. Babbar A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin Toxicol Pathol 40 2012 847 873
11. L. Brambilla, D. Genini, E. Laurini, J. Merulla, L. Perez, M. Fermeglia, G.M. Carbone, S. Pricl, and C.V. Catapano Hitting the right spot: mechanism of action of OPB-31121, a novel and potent inhibitor of the Signal Transducer and Activator of Transcription 3 (STAT3) Mol Oncol 9 2015 1194 1206
12. C. Buerger, K. Nagel-Wolfrum, C. Kunz, I. Wittig, K. Butz, F. Hoppe-Seyler, and B. Groner Sequence-specific peptide aptamers, interacting with the intracellular domain of the epidermal growth factor receptor, interfere with Stat3 activation and inhibit the growth of tumor cells J Biol Chem 278 2003 37610 37621
13. K.S. Chan, S. Sano, K. Kiguchi, J. Anders, N. Komazawa, J. Takeda, and J. DiGiovanni Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis J Clin Invest 114 2004 720 728
14. Q. Chang, E. Bournazou, P. Sansone, M. Berishaj, S.P. Gao, L. Daly, J. Wels, T. Theilen, S. Granitto, X. Zhang, J. Cotari, M.L. Alpaugh, E. de Stanchina, K. Manova, M. Li, M. Bonafe, C. Ceccarelli, M. Taffurelli, D. Santini, G. Altan-Bonnet, R. Kaplan, L. Norton, N. Nishimoto, D. Huszar, D. Lyden, and J. Bromberg The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis Neoplasia 15 2013 848 862
15. P.S. Chen, Y.W. Shih, H.C. Huang, and H.W. Cheng Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression PLoS ONE 6 2011 e20164
16. C.T. Chiang, T.D. Way, S.J. Tsai, and J.K. Lin Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation FEBS Lett 581 2007 5735 5742
17. A.W. Chua, H.S. Hay, P. Rajendran, M.K. Shanmugam, F. Li, P. Bist, E.S. Koay, L.H. Lim, A.P. Kumar, and G. Sethi Butein downregulates chemokine receptor CXCR4 expression and function through suppression of NF-kappaB activation in breast and pancreatic tumor cells Biochem Pharmacol 80 2010 1553 1562
18. A. Cort, and T. Ozben Natural product modulators to overcome multidrug resistance in cancer Nutr Cancer 2015 1 13
19. F.M. Corvinus, C. Orth, R. Moriggl, S.A. Tsareva, S. Wagner, E.B. Pfitzner, D. Baus, R. Kaufmann, L.A. Huber, K. Zatloukal, H. Beug, P. Ohlschlager, A. Schutz, K.J. Halbhuber, and K. Friedrich Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth Neoplasia 7 2005 545 555
20. L. Dai, L. Cheng, X. Zhang, Q. Jiang, S. Zhang, S. Wang, Y. Li, X. Chen, T. Du, Y. Yang, H. Tian, P. Fan, N. Yan, L. Dai, Y. Wei, and H. Deng Plasmid-based STAT3-siRNA efficiently inhibits breast tumor growth and metastasis in mice Neoplasma 58 2011 538 547
21. X. Dai, K.S. Ahn, C. Kim, K.S. Siveen, T.H. Ong, M.K. Shanmugam, F. Li, J. Shi, A.P. Kumar, L.Z. Wang, B.C. Goh, J. Magae, K.M. Hui, and G. Sethi Ascochlorin, an isoprenoid antibiotic inhibits growth and invasion of hepatocellular carcinoma by targeting STAT3 signaling cascade through the induction of PIAS3 Mol Oncol 9 2015 818 833
22. J.E. Darnell Jr. The JAK-STAT pathway: summary of initial studies and recent advances Recent Prog Horm Res 51 1996 391 403 (discussion 403-394)
23. J.E. Darnell Jr., I.M. Kerr, and G.R. Stark Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins Science 264 1994 1415 1421
24. A. Deguchi Curcumin targets in inflammation and cancer Endocr Metab Immune Disord Drug Targets 15 2015 88 96
25. A. Dhanik, J.S. McMurray, and L.E. Kavraki Binding modes of peptidomimetics designed to inhibit STAT3 PLoS ONE 7 2012 e51603
26. W. Du, J. Hong, Y.C. Wang, Y.J. Zhang, P. Wang, W.Y. Su, Y.W. Lin, R. Lu, W.P. Zou, H. Xiong, and J.Y. Fang Inhibition of JAK2/STAT3 signalling induces colorectal cancer cell apoptosis via mitochondrial pathway J Cell Mol Med 16 2012 1878 1888
27. F. Eddahri, S. Denanglaire, F. Bureau, R. Spolski, W.J. Leonard, O. Leo, and F. Andris Interleukin-6/STAT3 signaling regulates the ability of naive T cells to acquire B-cell help capacities Blood 113 2009 2426 2433
28. N. Ellison, C.L. Loprinzi, J. Kugler, A.K. Hatfield, A. Miser, J.A. Sloan, D.B. Wender, K.M. Rowland, R. Molina, T.L. Cascino, A.M. Vukov, H.S. Dhaliwal, and C. Ghosh Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients J Clin Oncol 15 1997 2974 2980
29. L.O. Flowers, P.S. Subramaniam, and H.M. Johnson A SOCS-1 peptide mimetic inhibits both constitutive and IL-6 induced activation of STAT3 in prostate cancer cells Oncogene 24 2005 2114 2120
30. S.L. Fossey, M.D. Bear, J. Lin, C. Li, E.B. Schwartz, P.K. Li, J.R. Fuchs, J. Fenger, W.C. Kisseberth, and C.A. London The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines BMC Cancer 11 2011 112
31. D.A. Frank STAT3 as a central mediator of neoplastic cellular transformation Cancer Lett 251 2007 199 210
32. Y. Fujisaka, Y. Onozawa, T. Kurata, H. Yasui, I. Goto, K. Yamazaki, N. Machida, J. Watanabe, H. Shimada, X. Shi, and N. Boku First report of the safety, tolerability, and pharmacokinetics of the Src kinase inhibitor saracatinib (AZD0530) in Japanese patients with advanced solid tumours Investig New Drugs 31 2013 108 114
33. M. Furqan, N. Mukhi, B. Lee, and D. Liu Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application Biol. Res. 1 2013 5
34. H. Gali-Muhtasib, A. Roessner, and R. Schneider-Stock Thymoquinone: A promising anti-cancer drug from natural sources Int J Biochem Cell Biol 38 2006 1249 1253
35. L.F. Gao, D.Q. Xu, Y.T. Shao, D. Zhao, and X.J. Zhao Knockdown of STAT3 expression using siRNA inhibits the growth of prostate cancer cell lines Zhonghua Nan Ke Xue 11 29-33 2005 37
36. L.F. Gao, D.Q. Xu, L.J. Wen, X.Y. Zhang, Y.T. Shao, and X.J. Zhao Inhibition of STAT3 expression by siRNA suppresses growth and induces apoptosis in laryngeal cancer cells Acta Pharmacol Sin 26 2005 377 383
37. M.B. Gariboldi, R. Ravizza, and E. Monti The IGFR1 inhibitor NVP-AEW541 disrupts a pro-survival and pro-Angiogenic IGF-STAT3-HIF1 pathway in human glioblastoma cells Biochem Pharmacol 80 2010 455 462
38. W. Glienke, L. Maute, J. Wicht, and L. Bergmann Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and downregulation of survivin/BIRC5 gene expression Cancer Investig 28 2010 166 171
39. G. Gritsina, F. Xiao, S.W. O'Brien, R. Gabbasov, M.A. Maglaty, R.H. Xu, R.J. Thapa, Y. Zhou, E. Nicolas, S. Litwin, S. Balachandran, L.J. Sigal, D. Huszar, and D.C. Connolly Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth Mol Cancer Ther 14 2015 1035 1047
40. Z. Han, J. Feng, Z. Hong, L. Chen, W. Li, S. Liao, X. Wang, T. Ji, S. Wang, D. Ma, G. Chen, and Q. Gao Silencing of the STAT3 signaling pathway reverses the inherent and induced chemoresistance of human ovarian cancer cells Biochem Biophys Res Commun 435 2013 188 194
41. F. Hayakawa, K. Sugimoto, Y. Harada, N. Hashimoto, N. Ohi, S. Kurahashi, and T. Naoe A novel STAT inhibitor, OPB-31121, has a significant antitumor effect on leukemia with STAT-Addictive oncokinases Blood Cancer J 3 2013 e166
42. Z. He, H. Chen, G. Li, H. Zhu, Y. Gao, L. Zhang, and J. Sun Diosgenin inhibits the migration of human breast cancer MDA-MB-231 cells by suppressing Vav2 activity Phytomedicine 21 2014 871 876
43. A. Herrmann, M. Vogt, M. Monnigmann, T. Clahsen, U. Sommer, S. Haan, V. Poli, P.C. Heinrich, and G. Muller-Newen Nucleocytoplasmic shuttling of persistently activated STAT3 J Cell Sci 120 2007 3249 3261
44. E. Hexner, G. Roboz, R. Hoffman, S. Luger, J. Mascarenhas, M. Carroll, R. Clementi, D. Bensen-Kennedy, and A. Moliterno Open-label study of oral CEP-701 (lestaurtinib) in patients with polycythaemia vera or essential thrombocythaemia with JAK2-V617F mutation Br J Haematol 164 2014 83 93
45. A. Hochhaus, and H. Kantarjian The development of dasatinib as a treatment for chronic myeloid leukemia (CML): from initial studies to application in newly diagnosed patients J Cancer Res Clin Oncol 139 2013 1971 1984
46. S.J. Hosseinimehr, and S.A. Hosseini Resveratrol sensitizes selectively thyroid cancer cell to 131-iodine toxicity J Toxicol 2014 2014 839597
47. C. Huang, T. Jiang, L. Zhu, J. Liu, J. Cao, K.J. Huang, and Z.J. Qiu STAT3-targeting RNA interference inhibits pancreatic cancer angiogenesis in vitro and in vivo Int J Oncol 38 2011 1637 1644
48. W. Huang, Z. Dong, F. Wang, H. Peng, J.Y. Liu, and J.T. Zhang A small molecule compound targeting STAT3 DNA-binding domain inhibits cancer cell proliferation, migration, and invasion ACS Chem Biol 9 2014 1188 1196
49. J.N. Ihle The Stat family in cytokine signaling Curr Opin Cell Biol 13 2001 211 217
50. P.A. Johnston, and J.R. Grandis STAT3 signaling: Anticancer strategies and challenges Mol Interv 11 2011 18 26
51. L.M. Judd, T.R. Menheniott, H. Ling, C.B. Jackson, M. Howlett, A. Kalantzis, W. Priebe, and A.S. Giraud Inhibition of the JAK2/STAT3 pathway reduces gastric cancer growth in vitro and in vivo PLoS ONE 9 2014 e95993
52. A. Junicho, T. Matsuda, T. Yamamoto, H. Kishi, K. Korkmaz, F. Saatcioglu, H. Fuse, and A. Muraguchi Protein inhibitor of activated STAT3 regulates androgen receptor signaling in prostate carcinoma cells Biochem Biophys Res Commun 278 2000 9 13
53. M.Z. Kamran, P. Patil, and R.P. Gude Role of STAT3 in cancer metastasis and translational advances Biomed Res Int 2013 2013 421821
54. R. Kannaiyan, H.S. Hay, P. Rajendran, F. Li, M.K. Shanmugam, S. Vali, T. Abbasi, S. Kapoor, A. Sharma, A.P. Kumar, W.J. Chng, and G. Sethi Celastrol inhibits proliferation and induces chemosensitization through down-regulation of NF-kappaB and STAT3 regulated gene products in multiple myeloma cells Br J Pharmacol 164 2011 1506 1521
55. E.C. Keystone, P.C. Taylor, E. Drescher, D.E. Schlichting, S.D. Beattie, P.Y. Berclaz, C.H. Lee, R.K. Fidelus-Gort, M.E. Luchi, T.P. Rooney, W.L. Macias, and M.C. Genovese Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate Ann Rheum Dis 74 2015 333 340
56. D.Y. Kim, S.T. Cha, D.H. Ahn, H.Y. Kang, C.I. Kwon, K.H. Ko, S.G. Hwang, P.W. Park, K.S. Rim, and S.P. Hong STAT3 expression in gastric cancer indicates a poor prognosis J Gastroenterol Hepatol 24 2009 646 651
57. E.S. Kim, S.Y. Hong, H.K. Lee, S.W. Kim, M.J. An, T.I. Kim, K.R. Lee, W.H. Kim, and J.H. Cheon Guggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells Oncol Rep 20 2008 1321 1327
58. M.J. Kim, H.J. Nam, H.P. Kim, S.W. Han, S.A. Im, T.Y. Kim, D.Y. Oh, and Y.J. Bang OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells Cancer Lett 335 2013 145 152
59. Y. Kim, H. Kang, S.W. Jang, and J. Ko Celastrol inhibits breast cancer cell invasion via suppression of NF-kB-mediated matrix metalloproteinase-9 expression Cell Physiol Biochem 28 2011 175 184
60. P. Kittakoop Anticancer drugs and potential anticancer leads inspired by natural products Chapter 5 R. Atta ur, Stud Nat Prod Chem Volume 44 2015 Elsevier 251 307
61. R.S. Komrokji, J.F. Seymour, A.W. Roberts, M. Wadleigh, L.B. To, R. Scherber, E. Turba, A. Dorr, J. Zhu, L. Wang, T. Granston, M.S. Campbell, and R.A. Mesa Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis Blood 125 2015 2649 2655
62. A. Kotha, M. Sekharam, L. Cilenti, K. Siddiquee, A. Khaled, A.S. Zervos, B. Carter, J. Turkson, and R. Jove Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein Mol Cancer Ther 5 2006 621 629
63. A. Kumar, and U. Bora Molecular docking studies on inhibition of Stat3 dimerization by curcumin natural derivatives and its conjugates with amino acids Bioinformation 8 2012 988 993
64. S. Kunigal, S.S. Lakka, P.K. Sodadasu, N. Estes, and J.S. Rao Stat3-siRNA induces Fas-mediated apoptosis in vitro and in vivo in breast cancer Int J Oncol 34 2009 1209 1220
65. C.K. Lau, Z.F. Yang, S.P. Lam, C.T. Lam, P. Ngai, K.H. Tam, R.T. Poon, and S.T. Fan Inhibition of Stat3 activity by YC-1 enhances chemo-sensitivity in hepatocellular carcinoma Cancer Biol Ther 6 2007 1900 1907
66. H.W. Lee, K.S. Jang, H.J. Choi, A. Jo, J.H. Cheong, and K.H. Chun Celastrol inhibits gastric cancer growth by induction of apoptosis and autophagy BMB Rep 47 2014 697 702
67. J.H. Lee, K.J. Choi, W.D. Seo, S.Y. Jang, M. Kim, B.W. Lee, J.Y. Kim, S. Kang, K.H. Park, Y.S. Lee, and S. Bae Enhancement of radiation sensitivity in lung cancer cells by celastrol is mediated by inhibition of Hsp90 Int J Mol Med 27 2011 441 446
68. J.H. Lee, C. Kim, G. Sethi, and K.S. Ahn Brassinin inhibits STAT3 signaling pathway through modulation of PIAS-3 and SOCS-3 expression and sensitizes human lung cancer xenograft in nude mice to paclitaxel Oncotarget 6 2015 6386 6405
69. M.H. Lee, J.K. Kundu, Y.S. Keum, Y.Y. Cho, Y.J. Surh, and B.Y. Choi Resveratrol inhibits IL-6-induced transcriptional activity of AR and STAT3 in human prostate cancer LNCaP-FGC cells Biomol Ther 22 2014 426 430 (Seoul)
70. R.J. Leeman, V.W. Lui, and J.R. Grandis STAT3 as a therapeutic target in head and neck cancer Expert Opin Biol Ther 6 2006 231 241
71. D.E. Levy, and C.K. Lee What does Stat3 do? J Clin Invest 109 2002 1143 1148
72. F. Li, P.P. Fernandez, P. Rajendran, K.M. Hui, and G. Sethi Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to suppression of proliferation and chemosensitization of human hepatocellular carcinoma cells Cancer Lett 292 2010 197 207
73. F. Li, P. Rajendran, and G. Sethi Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway Br J Pharmacol 161 2010 541 554
74. J. Li, J. Cui, J. Zhang, Y. Liu, L. Han, C. Jia, J. Deng, and H. Liang PIAS3, an inhibitor of STAT3, has intensively negative association with the survival of gastric cancer Int J Clin Exp 8 2015 682 689
75. Y. Li, W. Zhu, J. Li, M. Liu, and M. Wei Resveratrol suppresses the STAT3 signaling pathway and inhibits proliferation of high glucose-exposed HepG2 cells partly through SIRT1 Oncol Rep 30 2013 2820 2828
76. Z.W. Liang, B.F. Guo, Y. Li, X.J. Li, X. Li, L.J. Zhao, L.F. Gao, H. Yu, X.J. Zhao, L. Zhang, and B.X. Yang Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo Asian J Androl 13 2011 481 486
77. L. Lin, S. Deangelis, E. Foust, J. Fuchs, C. Li, P.K. Li, E.B. Schwartz, G.B. Lesinski, D. Benson, J. Lu, D. Hoyt, and J. Lin A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells Mol Cancer 9 2010 217
78. L. Lin, A. Liu, Z. Peng, H.J. Lin, P.K. Li, C. Li, and J. Lin STAT3 is necessary for proliferation and survival in colon cancer-initiating cells Cancer Res 71 2011 7226 7237
79. M. Lo Iacono, V. Monica, T. Vavala, M. Gisabella, S. Saviozzi, E. Bracco, S. Novello, M. Papotti, and G.V. Scagliotti ATF2 contributes to cisplatin resistance in non-small cell lung cancer and celastrol induces cisplatin resensitization through inhibition of JNK/ATF2 pathway Int J Cancer 136 2015 2598 2609
80. Z. Lu, Y. Jin, L. Qiu, Y. Lai, and J. Pan Celastrol, a novel HSP90 inhibitor, depletes Bcr-Abl and induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation Cancer Lett 290 2010 182 191
81. T. Luca, V. Barresi, G. Privitera, N. Musso, M. Caruso, D.F. Condorelli, and S. Castorina In vitro combined treatment with cetuximab and trastuzumab inhibits growth of colon cancer cells Cell Prolif 47 2014 435 447
82. G.G. Mackenzie, N. Queisser, M.L. Wolfson, C.G. Fraga, A.M. Adamo, and P.I. Oteiza Curcumin induces cell-Arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells Int J Cancer 123 2008 56 65
83. S.B. Mali Review of STAT3 (Signal Transducers and Activators of Transcription) in head and neck cancer Oral Oncol 51 2015 565 569
84. A.J. Marti-Carvajal, V. Anand, and I. Sola Janus kinase-1 and Janus kinase-2 inhibitors for treating myelofibrosis Cochrane Database Syst Rev 4 2015 (Cd010298)
85. A.J. Mead, D. Milojkovic, S. Knapper, M. Garg, J. Chacko, M. Farquharson, J. Yin, S. Ali, R.E. Clark, C. Andrews, M. Ktiouet Dawson, and C. Harrison Response to ruxolitinib in patients with intermediate-1-, intermediate-2-, and high-risk myelofibrosis: results of the UK ROBUST Trial Br J Haematol 170 2015 29 39
86. C. Mi, H. Shi, J. Ma, L.Z. Han, J.J. Lee, and X. Jin Celastrol induces the apoptosis of breast cancer cells and inhibits their invasion via downregulation of MMP-9 Oncol Rep 32 2014 2527 2532
87. M. Minami, M. Inoue, S. Wei, K. Takeda, M. Matsumoto, T. Kishimoto, and S. Akira STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line Proc Natl Acad Sci U S A 93 1996 3963 3966
88. N. Mo, Z.Q. Li, J. Li, and Y.D. Cao Curcumin inhibits TGF-beta1-induced MMP-9 and invasion through ERK and Smad signaling in breast cancer MDA- MB-231 cells Asian Pac. J. Cancer Prev. 13 2012 5709 5714
89. C.D. Mohan, H. Bharathkumar, K.C. Bulusu, V. Pandey, S. Rangappa, J.E. Fuchs, M.K. Shanmugam, X. Dai, F. Li, A. Deivasigamani, K.M. Hui, A.P. Kumar, P.E. Lobie, A. Bender, Sethi G. Basappa, and K.S. Rangappa Development of a novel azaspirane that targets the Janus kinase-signal transducer and activator of transcription (STAT) pathway in hepatocellular carcinoma in vitro and in vivo J Biol Chem 289 2014 34296 34307
90. T. Morikawa, Y. Baba, M. Yamauchi, A. Kuchiba, K. Nosho, K. Shima, N. Tanaka, C. Huttenhower, D.A. Frank, C.S. Fuchs, and S. Ogino STAT3 expression, molecular features, inflammation patterns, and prognosis in a database of 724 colorectal cancers Clin Cancer Res 17 2011 1452 1462
91. C. Moser, P. Schachtschneider, S.A. Lang, A. Gaumann, A. Mori, J. Zimmermann, H.J. Schlitt, E.K. Geissler, and O. Stoeltzing Inhibition of insulin-like growth factor-I receptor (IGF-IR) using NVP-AEW541, a small molecule kinase inhibitor, reduces orthotopic pancreatic cancer growth and angiogenesis Eur J Cancer 44 2008 1577 1586
92. A.K. Mukherjee, S. Basu, N. Sarkar, and A.C. Ghosh Advances in cancer therapy with plant based natural products Curr Med Chem 8 2001 1467 1486
93. T. Murakami, N. Takigawa, T. Ninomiya, N. Ochi, M. Yasugi, Y. Honda, T. Kubo, E. Ichihara, K. Hotta, M. Tanimoto, and K. Kiura Effect of AZD1480 in an epidermal growth factor receptor-driven lung cancer model Lung Cancer 83 2014 30 36
94. K. Nagel-Wolfrum, C. Buerger, I. Wittig, K. Butz, F. Hoppe-Seyler, and B. Groner The interaction of specific peptide aptamers with the DNA binding domain and the dimerization domain of the transcription factor Stat3 inhibits transactivation and induces apoptosis in tumor cells Mol Cancer Res 2 2004 170 182
95. R.I. Nicholson, J.M. Gee, and M.E. Harper EGFR and cancer prognosis Eur J Cancer 37 Suppl. 4 2001 S9 S15
96. D.Y. Oh, S.H. Lee, S.W. Han, M.J. Kim, T.M. Kim, T.Y. Kim, D.S. Heo, M. Yuasa, Y. Yanagihara, and Y.J. Bang Phase I study of OPB-31121, an oral STAT3 inhibitor, in patients with advanced solid tumors Cancer Res Treat 47 2015 607 615
97. E. Ojima, T. Nakano, A. Kanamoto, and S. Sasaki A case of advanced colon cancer successfully treated with combination therapy of cetuximab and oxaliplatin, leucovorin, and 5-fluorouracil Gan To Kagaku Ryoho 40 2013 1962 1964
98. T. Okusaka, H. Ueno, M. Ikeda, S. Mitsunaga, M. Ozaka, H. Ishii, O. Yokosuka, Y. Ooka, R. Yoshimoto, Y. Yanagihara, and K. Okita Phase 1 and pharmacological trial of OPB-31121, a signal transducer and activator of transcription-3 inhibitor, in patients with advanced hepatocellular carcinoma Hepatol Res 45 2015 1283 1291
99. A. Olivera, T.W. Moore, F. Hu, A.P. Brown, A. Sun, D.C. Liotta, J.P. Snyder, Y. Yoon, H. Shim, A.I. Marcus, A.H. Miller, and T.W. Pace Inhibition of the NF-kappaB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): Anti-inflammatory and anti-cancer properties Int Immunopharmacol 12 2012 368 377
100. Y. Pan, F. Zhou, R. Zhang, and F.X. Claret Stat3 inhibitor Stattic exhibits potent antitumor activity and induces chemo- and radio-sensitivity in nasopharyngeal carcinoma PLoS ONE 8 2013 e54565
101. M.K. Pandey, B. Sung, K.S. Ahn, and B.B. Aggarwal Butein suppresses constitutive and inducible signal transducer and activator of transcription (STAT) 3 activation and STAT3-regulated gene products through the induction of a protein tyrosine phosphatase SHP-1 Mol Pharmacol 75 2009 525 533
102. A. Pardanani, R.R. Laborde, T.L. Lasho, C. Finke, K. Begna, A. Al-Kali, W.J. Hogan, M.R. Litzow, A. Leontovich, M. Kowalski, and A. Tefferi Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis Leukemia 27 2013 1322 1327
103. E.R. Plimack, P.M. Lorusso, P. McCoon, W. Tang, A.D. Krebs, G. Curt, and S.G. Eckhardt AZD1480: A phase I study of a novel JAK2 inhibitor in solid tumors Oncologist 18 2013 819 820
104. E. Pozo-Guisado, J.M. Merino, S. Mulero-Navarro, M.J. Lorenzo-Benayas, F. Centeno, A. Alvarez-Barrientos, and P.M. Fernandez-Salguero Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-kappaB Int J Cancer 115 2005 74 84
105. A.L. Pranada, S. Metz, A. Herrmann, P.C. Heinrich, and G. Muller-Newen Real time analysis of STAT3 nucleocytoplasmic shuttling J Biol Chem 279 2004 15114 15123
106. K.M. Quesnelle, A.L. Boehm, and J.R. Grandis STAT-mediated EGFR signaling in cancer J Cell Biochem 102 2007 311 319
107. P. Rajendran, F. Li, K.A. Manu, M.K. Shanmugam, S.Y. Loo, A.P. Kumar, and G. Sethi gamma-Tocotrienol is a novel inhibitor of constitutive and inducible STAT3 signalling pathway in human hepatocellular carcinoma: potential role as an antiproliferative, pro-Apoptotic and chemosensitizing agent Br J Pharmacol 163 2011 283 298
108. P. Rajendran, F. Li, M.K. Shanmugam, R. Kannaiyan, J.N. Goh, K.F. Wong, W. Wang, E. Khin, V. Tergaonkar, A.P. Kumar, J.M. Luk, and G. Sethi Celastrol suppresses growth and induces apoptosis of human hepatocellular carcinoma through the modulation of STAT3/JAK2 signaling cascade in vitro and in vivo Cancer Prev Res (Phila) 5 2012 631 643
109. P. Rajendran, T.H. Ong, L. Chen, F. Li, M.K. Shanmugam, S. Vali, T. Abbasi, S. Kapoor, A. Sharma, A.P. Kumar, K.M. Hui, and G. Sethi Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo Clin Cancer Res 17 2011 1425 1439
110. N.C. Reich, and L. Liu Tracking STAT nuclear traffic Nat Rev Immunol 6 2006 602 612
111. W.D. Rollyson, C.A. Stover, K.C. Brown, H.E. Perry, C.D. Stevenson, C.A. McNees, J.G. Ball, M.A. Valentovic, and P. Dasgupta Bioavailability of capsaicin and its implications for drug delivery J Control Release 196 2014 96 105
112. M. Sakaguchi, M. Oka, T. Iwasaki, Y. Fukami, and C. Nishigori Role and regulation of STAT3 phosphorylation at Ser727 in melanocytes and melanoma cells J Invest Dermatol 132 2012 1877 1885
113. M. Santoni, F. Massari, M. Del Re, C. Ciccarese, F. Piva, G. Principato, R. Montironi, D. Santini, R. Danesi, G. Tortora, and S. Cascinu Investigational therapies targeting signal transducer and activator of transcription 3 for the treatment of cancer Expert Opin Investig Drugs 2015 1 16
114. F.P. Santos, H.M. Kantarjian, N. Jain, T. Manshouri, D.A. Thomas, G. Garcia-Manero, D. Kennedy, Z. Estrov, J. Cortes, and S. Verstovsek Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis Blood 115 6 2010 1131 1136
115. M. Saydmohammed, D. Joseph, and V. Syed Curcumin suppresses constitutive activation of STAT-3 by up-regulating protein inhibitor of activated STAT-3 (PIAS-3) in ovarian and endometrial cancer cells J Cell Biochem 110 2010 447 456
116. R. Schneider-Stock, I.H. Fakhoury, A.M. Zaki, C.O. El-Baba, and H.U. Gali-Muhtasib Thymoquinone: fifty years of success in the battle against cancer models Drug Discov Today 19 2014 18 30
117. A. Scuto, P. Krejci, L. Popplewell, J. Wu, Y. Wang, M. Kujawski, C. Kowolik, H. Xin, L. Chen, Y. Wang, L. Kretzner, H. Yu, W.R. Wilcox, Y. Yen, S. Forman, and R. Jove The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival Leukemia 25 2011 538 550
118. C.K. Sen, S. Khanna, C. Rink, and S. Roy Tocotrienols: The emerging face of natural vitamin E Vitam Horm 76 2007 203 261
119. C.K. Sen, S. Khanna, and S. Roy Tocotrienols in health and disease: The other half of the natural vitamin E family Mol Aspects Med 28 2007 692 728
120. M. Sen, N.I. Pollock, J. Black, K.A. DeGrave, S. Wheeler, M.L. Freilino, S. Joyce, V.W. Lui, Y. Zeng, S.I. Chiosea, and J.R. Grandis JAK kinase inhibition abrogates STAT3 activation and head and neck squamous cell carcinoma tumor growth Neoplasia 17 2015 256 264
121. M. Sen, S.M. Thomas, S. Kim, J.I. Yeh, R.L. Ferris, J.T. Johnson, U. Duvvuri, J. Lee, N. Sahu, S. Joyce, M.L. Freilino, H. Shi, C. Li, D. Ly, S. Rapireddy, J.P. Etter, P.K. Li, L. Wang, S. Chiosea, R.R. Seethala, W.E. Gooding, X. Chen, N. Kaminski, K. Pandit, D.E. Johnson, and J.R. Grandis First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy Cancer Discov 2 2012 694 705
122. G. Sethi, S. Chatterjee, P. Rajendran, F. Li, M.K. Shanmugam, K.F. Wong, A.P. Kumar, P. Senapati, A.K. Behera, K.M. Hui, J. Basha, N. Natesh, J.M. Luk, and T.K. Kundu Inhibition of STAT3 dimerization and acetylation by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo Mol Cancer 13 2014 66
123. M.K. Shanmugam, R. Kannaiyan, and G. Sethi Targeting cell signaling and apoptotic pathways by dietary agents: role in the prevention and treatment of cancer Nutr Cancer 63 2011 161 173
124. M.K. Shanmugam, G. Rane, M.M. Kanchi, F. Arfuso, A. Chinnathambi, M.E. Zayed, S.A. Alharbi, B.K. Tan, A.P. Kumar, and G. Sethi The multifaceted role of curcumin in cancer prevention and treatment Molecules 20 2015 2728 2769
125. W. Shao, A. Paul, S. Abbasi, P.S. Chahal, J.A. Mena, J. Montes, A. Kamen, and S. Prakash A novel polyethyleneimine-coated adeno-Associated virus-like particle formulation for efficient siRNA delivery in breast cancer therapy: preparation and in vitro analysis Int J Nanomedicine 7 2012 1575 1586
126. A. Shodeinde, K. Ginjupalli, H.D. Lewis, S. Riaz, and B.E. Barton STAT3 inhibition induces apoptosis in cancer cells independent of STAT1 or STAT2 J Mol Biochem 2 2013 18 26
127. A.M. Siegel, J. Heimall, A.F. Freeman, A.P. Hsu, E. Brittain, J.M. Brenchley, D.C. Douek, G.H. Fahle, J.I. Cohen, S.M. Holland, and J.D. Milner A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory Immunity 35 2011 806 818
128. K.S. Siveen, A.H. Nguyen, J.H. Lee, F. Li, S.S. Singh, A.P. Kumar, G. Low, S. Jha, V. Tergaonkar, K.S. Ahn, and G. Sethi Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells Br J Cancer 111 2014 1327 1337
129. K.S. Siveen, S. Sikka, R. Surana, X. Dai, J. Zhang, A.P. Kumar, B.K. Tan, G. Sethi, and A. Bishayee Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors Biochim Biophys Acta 1845 2014 136 154
130. N. Song, S. Liu, J. Zhang, J. Liu, L. Xu, Y. Liu, and X. Qu Cetuximab-induced MET activation acts as a novel resistance mechanism in colon cancer cells Int J Mol Sci 15 2014 5838 5851
131. I. Souissi, I. Najjar, L. Ah-Koon, P.O. Schischmanoff, D. Lesage, S. Le Coquil, C. Roger, I. Dusanter-Fourt, N. Varin-Blank, A. Cao, V. Metelev, F. Baran-Marszak, and R. Fagard A STAT3-decoy oligonucleotide induces cell death in a human colorectal carcinoma cell line by blocking nuclear transfer of STAT3 and STAT3-bound NF-kappaB BMC Cell Biol 12 2011 14
132. A. Steinbach, S.M. Clark, and A.B. Clemmons Bosutinib: A novel src/abl kinase inhibitor for chronic myelogenous leukemia J Adv Pract Oncol 4 2013 451 455
133. A. Subramaniam, M.K. Shanmugam, T.H. Ong, F. Li, E. Perumal, L. Chen, S. Vali, T. Abbasi, S. Kapoor, K.S. Ahn, A.P. Kumar, K.M. Hui, and G. Sethi Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3 Br J Pharmacol 170 2013 807 821
134. A. Subramaniam, M.K. Shanmugam, E. Perumal, F. Li, A. Nachiyappan, X. Dai, S.N. Swamy, K.S. Ahn, A.P. Kumar, B.K. Tan, K.M. Hui, and G. Sethi Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma Biochim Biophys Acta 1835 2013 46 60
135. B. Sung, A.B. Kunnumakkara, G. Sethi, P. Anand, S. Guha, and B.B. Aggarwal Curcumin circumvents chemoresistance in vitro and potentiates the effect of thalidomide and bortezomib against human multiple myeloma in nude mice model Mol Cancer Ther 8 2009 959 970
136. K. Takeda, K. Noguchi, W. Shi, T. Tanaka, M. Matsumoto, N. Yoshida, T. Kishimoto, and S. Akira Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality Proc Natl Acad Sci U S A 94 1997 3801 3804
137. F.Y. Tang, Y.C. Su, N.C. Chen, H.S. Hsieh, and K.S. Chen Resveratrol inhibits migration and invasion of human breast-cancer cells Mol Nutr Food Res 52 2008 683 691
138. B. Thyagarajan, N. Krivitskaya, J.G. Potian, K. Hognason, C.C. Garcia, and J.J. McArdle Capsaicin protects mouse neuromuscular junctions from the neuroparalytic effects of botulinum neurotoxin a J Pharmacol Exp Ther 331 2009 361 371
139. W. Tian, B. Li, X. Zhang, W. Dang, X. Wang, H. Tang, L. Wang, H. Cao, and T. Chen Suppression of tumor invasion and migration in breast cancer cells following delivery of siRNA against Stat3 with the antimicrobial peptide PR39 Oncol Rep 28 2012 1362 1368
140. O.A. Timofeeva, V. Gaponenko, S.J. Lockett, S.G. Tarasov, S. Jiang, C.J. Michejda, A.O. Perantoni, and N.I. Tarasova Rationally designed inhibitors identify STAT3 N-domain as a promising anticancer drug target ACS Chem Biol 2 2007 799 809
141. O.A. Timofeeva, N.I. Tarasova, X. Zhang, S. Chasovskikh, A.K. Cheema, H. Wang, M.L. Brown, and A. Dritschilo STAT3 suppresses transcription of proapoptotic genes in cancer cells with the involvement of its N-terminal domain Proc Natl Acad Sci U S A 110 2013 1267 1272
142. M.J. Tuorkey Curcumin a potent cancer preventive agent: mechanisms of cancer cell killing Interv Med Appl Sci 6 2014 139 146
143. J. Turkson, J.S. Kim, S. Zhang, J. Yuan, M. Huang, M. Glenn, E. Haura, S. Sebti, A.D. Hamilton, and R. Jove Novel peptidomimetic inhibitors of signal transducer and activator of transcription 3 dimerization and biological activity Mol Cancer Ther 3 2004 261 269
144. N.A. Venier, A.J. Colquhoun, H. Sasaki, A. Kiss, L. Sugar, H. Adomat, N.E. Fleshner, L.H. Klotz, and V. Venkateswaran Capsaicin: A novel radio-sensitizing agent for prostate cancer Prostate 75 2015 113 125
145. S. Verstovsek, R. Hoffman, J. Mascarenhas, J.C. Soria, R. Bahleda, P. McCoon, W. Tang, J. Cortes, H. Kantarjian, and V. Ribrag A phase I, open-label, multi-center study of the JAK2 inhibitor AZD1480 in patients with myelofibrosis Leuk Res 39 2015 157 163
146. A. Vyas, P. Dandawate, S. Padhye, A. Ahmad, and F. Sarkar Perspectives on new synthetic curcumin analogs and their potential anticancer properties Curr Pharm Des 19 2013 2047 2069
147. S.W. Wang, J. Hu, Q.H. Guo, Y. Zhao, J.J. Cheng, D.S. Zhang, Q. Fei, J. Li, and Y.M. Sun AZD1480, a JAK inhibitor, inhibits cell growth and survival of colorectal cancer via modulating the JAK2/STAT3 signaling pathway Oncol Rep 32 2014 1991 1998
148. X. Wang, Y. Zhang, X. Zhang, W. Tian, W. Feng, and T. Chen The curcumin analogue hydrazinocurcumin exhibits potent suppressive activity on carcinogenicity of breast cancer cells via STAT3 inhibition Int J Oncol 40 2012 1189 1195
149. G. Wcislo Chapter 95 - resveratrol inhibitory effects against a malignant tumor: A molecular introductory review R.R. Watson, V.R. Preedy, S. Zibadi, Polyphenols in human health and disease 2014 Academic Press San Diego 1269 1281
150. A. Weber, C. Borghouts, N. Delis, L. Mack, B. Brill, A.C. Bernard, O. Coqueret, and B. Groner Inhibition of Stat3 by peptide aptamer rS3-PA enhances growth suppressive effects of irinotecan on colorectal cancer cells Horm Mol Biol Clin Invest 10 2012 273 279
151. P. Weerasinghe, G.E. Garcia, Q. Zhu, P. Yuan, L. Feng, L. Mao, and N. Jing Inhibition of Stat3 activation and tumor growth suppression of non-small cell lung cancer by G-quartet oligonucleotides Int J Oncol 31 2007 129 136
152. P. Weerasinghe, Y. Li, Y. Guan, R. Zhang, D.J. Tweardy, and N. Jing T40214/PEI complex: A potent therapeutics for prostate cancer that targets STAT3 signaling Prostate 68 2008 1430 1442
153. V. Wiwanitkit Capsaicin induces apoptosis of cisplatin-resistant stomach cancer cells Nutr Cancer 64 2012 781
154. A.L. Wong, R.A. Soo, D.S. Tan, S.C. Lee, J.S. Lim, P.C. Marban, L.R. Kong, Y.J. Lee, L.Z. Wang, W.L. Thuya, R. Soong, M.Q. Yee, T.M. Chin, M.T. Cordero, B.R. Asuncion, B. Pang, S. Pervaiz, J.L. Hirpara, A. Sinha, W.W. Xu, M. Yuasa, T. Tsunoda, M. Motoyama, T. Yamauchi, and B.C. Goh Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies Ann Oncol 26 2015 998 1005
155. C.C. Woo, A. Hsu, A.P. Kumar, G. Sethi, and K.H. Tan Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer xenograft mouse model: The role of p38 MAPK and ROS PLoS ONE 8 2013 e75356
156. C.C. Woo, A.P. Kumar, G. Sethi, and K.H. Tan Thymoquinone: potential cure for inflammatory disorders and cancer Biochem Pharmacol 83 2012 443 451
157. A. Xiong, Z. Yang, Y. Shen, J. Zhou, and Q. Shen Transcription factor STAT3 as a novel molecular target for cancer prevention Cancers (Basel) 6 2014 926 957
158. X. Xu, J. Qin, and W. Liu Curcumin inhibits the invasion of thyroid cancer cells via down-regulation of PI3K/Akt signaling pathway Gene 546 2014 226 232
159. Y. Yakata, T. Nakayama, A. Yoshizaki, T. Kusaba, K. Inoue, and I. Sekine Expression of p-STAT3 in human gastric carcinoma: significant correlation in tumour invasion and prognosis Int J Oncol 30 2007 437 442
160. S. Yan, Z. Li, and C.J. Thiele Inhibition of STAT3 with orally active JAK inhibitor, AZD1480, decreases tumor growth in neuroblastoma and pediatric sarcomas in vitro and in vivo Oncotarget 4 2013 433 445
161. T.A. Yap, C.P. Carden, and S.B. Kaye Beyond chemotherapy: Targeted therapies in ovarian cancer Nat Rev Cancer 9 2009 167 181
162. A. Younes, J. Romaguera, M. Fanale, P. McLaughlin, F. Hagemeister, A. Copeland, S. Neelapu, L. Kwak, J. Shah, S. de Castro Faria, S. Hart, J. Wood, R. Jayaraman, K. Ethirajulu, and J. Zhu Phase I study of a novel oral Janus kinase 2 inhibitor, SB1518, in patients with relapsed lymphoma: evidence of clinical and biologic activity in multiple lymphoma subtypes J Clin Oncol 30 2012 4161 4167
163. P. Yoysungnoen-Chintana, P. Bhattarakosol, and S. Patumraj Antitumor and antiangiogenic activities of curcumin in cervical cancer xenografts in nude mice Biomed Res Int 2014 2014 817972
164. P. Zhang, H. Li, B. Yang, F. Yang, L.L. Zhang, Q.Y. Kong, X.Y. Chen, M.L. Wu, and J. Liu Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells Genes Cancer 5 2014 154 164
165. X. Zhang, P. Liu, B. Zhang, H. Mao, L. Shen, and Y. Ma Inhibitory effects of STAT3 decoy oligodeoxynucleotides on human epithelial ovarian cancer cell growth in vivo Int J Mol Med 32 2013 623 628
166. X. Zhang, Y. Sun, R. Pireddu, H. Yang, M.K. Urlam, H.R. Lawrence, W.C. Guida, N.J. Lawrence, and S.M. Sebti A novel inhibitor of STAT3 homodimerization selectively suppresses STAT3 activity and malignant transformation Cancer Res 73 2013 1922 1933
167. X. Zhou, Y. Ren, A. Liu, R. Jin, Q. Jiang, Y. Huang, L. Kong, X. Wang, and L. Zhang WP1066 sensitizes oral squamous cell carcinoma cells to cisplatin by targeting STAT3/miR-21 axis Sci Rep 4 2014 7461