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Expert Opinion on Investigational Drugs Volume 18, 2009 - Issue 1
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Review

Targeting STAT3 in cancer: how successful are we?

Peibin Yue University of Central Florida College of Medicine, Burnett School of Biomedical Sciences, Biomolecular Science Center, Department of Molecular Biology and Microbiology, 12722 Research Parkway, Orlando, FL 32826, USA +1 407 882 2250; +1 407 384 2062; [email protected]
, MD PhD &
James Turkson University of Central Florida College of Medicine, Burnett School of Biomedical Sciences, Biomolecular Science Center, Department of Molecular Biology and Microbiology, 12722 Research Parkway, Orlando, FL 32826, USA +1 407 882 2250; +1 407 384 2062; [email protected]
, PhD
Pages 45-56 | Published online: 21 Nov 2008

Bibliography

  • Darnell JE Jr. STATs and gene regulation. Science 1997;277(5332):1630-5
  • Turkson J. STAT proteins as novel targets for cancer drug discovery. Expert Opin Ther Targets 2004;8(5):409-22
  • Schroder M, Kroeger KM, Volk HD, et al. Preassociation of nonactivated STAT3 molecules demonstrated in living cells using bioluminescence resonance energy transfer: a new model of STAT activation? J Leukoc Biol 2004;75(5):792-7
  • Sehgal PB. Paradigm shifts in the cell biology of STAT signaling. Semin Cell Dev Biol 2008;19:329-40
  • Liu L, McBride KM, Reich NC. STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-alpha3. Proc Natl Acad Sci USA 2005;102(23):8150-5
  • Haura EB, Turkson J, Jove R. Mechanisms of disease: Insights into the emerging role of signal transducers and activators of transcription in cancer. Nat Clin Pract Oncol 2005;2(6):315-24
  • Kortylewski M, Kujawski M, Wang T, et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med 2005;11(12):1314-21
  • Kortylewski M, Yu H. Stat3 as a potential target for cancer immunotherapy. J Immunother 2007;30(2):131-9
  • Yu H, Jove R. The STATs of cancer: new molecular targets come of age. Nat Rev Cancer 2004;4(2):97-105
  • Darnell JE. Validating Stat3 in cancer therapy. Nat Med 2005;11(6):595-6
  • 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 USA 2007;104(18):7391-6
  • Siddiquee KA, Gunning PT, Glenn M, et al. An oxazole-based small-molecule Stat3 inhibitor modulates Stat3 stability and processing and induces antitumor cell effects. ACS Chem Biol 2007;2(12):787-98
  • Jing N, Zhu Q, Yuan P, et al. Targeting signal transducer and activator of transcription 3 with G-quartet oligonucleotides: a potential novel therapy for head and neck cancer. Mol Cancer Ther 2006;5(2):279-86
  • Weerasinghe P, Garcia GE, Zhu Q, et al. Inhibition of Stat3 activation and tumor growth suppression of non-small cell lung cancer by G-quartet oligonucleotides. Int J Oncol 2007;31(1):129-36
  • Turkson J, Ryan D, Kim JS, et al. Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation. J Biol Chem 2001;276(48):45443-55
  • McMurray JS. A new small-molecule Stat3 inhibitor. Chem Biol 2006;13(11):1123-4
  • Vultur A, Cao J, Arulanandam R, et al. Cell-to-cell adhesion modulates Stat3 activity in normal and breast carcinoma cells. Oncogene 2004;2315:2600-16
  • 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(1):48-54
  • Bhattacharya S, Ray RM, Johnson LR. STAT3-mediated transcription of Bcl-2, Mcl-1 and c-IAP2 prevents apoptosis in polyamine-depleted cells. Biochem J 2005;392(Pt 2):335-44
  • Turkson J, Kim JS, Zhang S, et al. Novel peptidomimetic inhibitors of signal transducer and activator of transcription 3 dimerization and biological activity. Mol Cancer Ther 2004;3(3):261-9
  • Ren Z, Cabell LA, Schaefer TS, McMurray JS. Identification of a high-affinity phosphopeptide inhibitor of Stat3. Bioorg Med Chem Lett 2003;13(4):633-6
  • 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(21):6661-70
  • Buerger C, Nagel-Wolfrum K, Kunz C, et al. 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 2003;278(39):37610-21
  • Nagel-Wolfrum K, Buerger C, Wittig I, et al. 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 2004;2(3):170-82
  • 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(13):4700-5
  • 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
  • Bhasin D, Cisek K, Pandharkar T, et al. Design, synthesis, and studies of small molecule STAT3 inhibitors. Bioorg Med Chem Lett 2008;18(1):391-5
  • Schust J, Sperl B, Hollis A, et al. Stattic: a small-molecule inhibitor of STAT3 activation and dimerization. Chem Biol 2006;13(11):1235-42
  • Hao W, Hu Y, Niu C, et al. Discovery of the catechol structural moiety as a Stat3 SH2 domain inhibitor by virtual screening. Bioorg Med Chem Lett 2008;18(18):4988-92
  • Turkson J, Zhang S, Mora LB, et al. A novel platinum compound inhibits constitutive Stat3 signaling and induces cell cycle arrest and apoptosis of malignant cells. J Biol Chem 2005;280(38):32979-88
  • Turkson J, Zhang S, Palmer J, et al. Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity. Mol Cancer Ther 2004;3(12):1533-42
  • Weidler M, Rether J, Anke T, Erkel G. Inhibition of interleukin-6 signaling by galiellalactone. FEBS Lett 2000;484(1):1-6
  • Hellsten R, Johansson M, Dahlman A, et al. Galiellalactone is a novel therapeutic candidate against hormone-refractory prostate cancer expressing activated Stat3. Prostate 2008;68(3):269-80
  • Borghouts C, Kunz C, Delis N, Groner B. Monomeric recombinant peptide aptamers are required for efficient intracellular uptake and target inhibition. Mol Cancer Res 2008;6(2):267-81
  • Gao L, Zhang L, Hu J, et al. Down-regulation of signal transducer and activator of transcription 3 expression using vector-based small interfering RNAs suppresses growth of human prostate tumor in vivo. Clin Cancer Res 2005;11(17):6333-41
  • Konnikova L, Kotecki M, Kruger MM, Cochran BH. Knockdown of STAT3 expression by RNAi induces apoptosis in astrocytoma cells. BMC Cancer 2003;3:23
  • Ling X, Arlinghaus RB. Knockdown of STAT3 expression by RNA interference inhibits the induction of breast tumors in immunocompetent mice. Cancer Res 2005;65(7):2532-6
  • Son G, Iimuro Y, Seki E, et al. Selective inactivation of NF-kappaB in the liver using NF-kappaB decoy suppresses CCl4-induced liver injury and fibrosis. Am J Physiol Gastrointest Liver Physiol 2007;293(3):G631-9
  • Bezzerri V, Borgatti M, Nicolis E, et al. Transcription factor oligodeoxynucleotides to NF-kappaB inhibit transcription of IL-8 in bronchial cells. Am J Respir Cell Mol Biol 2008;39(1):86-96
  • Moriyama I, Ishihara S, Rumi MA, et al. Decoy oligodeoxynucleotide targeting activator protein-1 (AP-1) attenuates intestinal inflammation in murine experimental colitis. Lab Invest 2008;88(6):652-63
  • Tomita N, Ogihara T, Morishita R. Transcription factors as molecular targets: molecular mechanisms of decoy ODN and their design. Curr Drug Targets 2003;4(8):603-8
  • Leong PL, Andrews GA, Johnson DE, et al. Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth. Proc Natl Acad Sci USA 2003;100(7):4138-43
  • Barton BE, Murphy TF, Shu P, et al. Novel single-stranded oligonucleotides that inhibit signal transducer and activator of transcription 3 induce apoptosis in vitro and in vivo in prostate cancer cell lines. Mol Cancer Ther 2004;3(10):1183-91
  • 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 NY Acad Sci 2006;1091:151-69
  • Sun X, Zhang J, Wang L, Tian Z. Growth inhibition of human hepatocellular carcinoma cells by blocking STAT3 activation with decoy-ODN. Cancer Lett 2008;262(2):201-13
  • Zhang X, Zhang J, Wang L, et al. Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice. BMC Cancer 2007;7:149
  • Xi S, Gooding WE, Grandis JR. In vivo antitumor efficacy of STAT3 blockade using a transcription factor decoy approach: implications for cancer therapy. Oncogene 2005;24(6):970-9
  • Morishita R, Aoki M, Ogihara T. Does gene therapy become pharmacotherapy? Exp Physiol 2005;90(3):307-13
  • Jing N, Li Y, Xu X, et al. Targeting Stat3 with G-quartet oligodeoxynucleotides in human cancer cells. DNA Cell Biol 2003;22(11):685-96
  • Zhu Q, Jing N. Computational study on mechanism of G-quartet oligonucleotide T40214 selectively targeting Stat3. J Comput Aided Mol Des 2007;21(10-11):641-8
  • Jing N, Li Y, Xiong W, et al. G-quartet oligonucleotides: a new class of signal transducer and activator of transcription 3 inhibitors that suppresses growth of prostate and breast tumors through induction of apoptosis. Cancer Res 2004;64(18):6603-9
  • Becker S, Groner B, Muller CW. Three-dimensional structure of the Stat3beta homodimer bound to DNA. Nature 1998;394(6689):145-51
  • Timofeeva OA, Gaponenko V, Lockett SJ, et al. Rationally designed inhibitors identify STAT3 N-domain as a promising anticancer drug target. ACS Chem Biol 2007;2(12):799-809
  • Blaskovich MA, Sun J, Cantor A, et al. Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res 2003;63(6):1270-9
  • van Kester MS, Out-Luiting JJ, von dem Borne PA, et al. Cucurbitacin I inhibits Stat3 and induces apoptosis in Sezary cells. J Invest Dermatol 2008;128(7):1691-5
  • Shi X, Franko B, Frantz C, et al. JSI-124 (cucurbitacin I) inhibits Janus kinase-3/signal transducer and activator of transcription-3 signalling, downregulates nucleophosmin-anaplastic lymphoma kinase (ALK), and induces apoptosis in ALK-positive anaplastic large cell lymphoma cells. Br J Haematol 2006;135(1):26-32
  • Su Y, Li G, Zhang X, et al. JSI-124 Inhibits Glioblastoma Multiforme Cell Proliferation through G2/M Cell Cycle Arrest and Apoptosis Augment. Cancer Biol Ther 2008;7(8):1243-9
  • Nefedova Y, Nagaraj S, Rosenbauer A, et al. Regulation of dendritic cell differentiation and antitumor immune response in cancer by pharmacologic-selective inhibition of the janus-activated kinase 2/signal transducers and activators of transcription 3 pathway. Cancer Res 2005;65(20):9525-35
  • Sun J, Blaskovich MA, Jove R, et al. a selective STAT3 activation inhibitor with potent antitumor activity. Oncogene 2005;24(20):3236-45
  • Liu T, Zhang M, Zhang H, et al. Combined antitumor activity of cucurbitacin B and docetaxel in laryngeal cancer. Eur J Pharmacol 2008;587(1-3):78-84
  • Tannin-Spitz T, Grossman S, Dovrat S, et al. Growth inhibitory activity of cucurbitacin glucosides isolated from Citrullus colocynthis on human breast cancer cells. Biochem Pharmacol 2007;73(1):56-67
  • Levitzki A. Tyrphostins: tyrosine kinase blockers as novel antiproliferative agents and dissectors of signal transduction. FASEB J 1992;6(14):3275-82
  • Ferrajoli A, Faderl S, Van Q, et al. WP1066 disrupts Janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells. Cancer Res 2007;67(23):11291-9
  • 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(17):2435-44
  • Pardanani A, Hood J, Lasho T, et al. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia 2007;21(8):1658-68
  • Kotha A, Sekharam M, Cilenti L, et al. Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein. Mol Cancer Ther 2006;5(3):621-9
  • Nam S, Buettner R, Turkson J, et al. Indirubin derivatives inhibit Stat3 signaling and induce apoptosis in human cancer cells. Proc Natl Acad Sci USA 2005;102(17):5998-6003
  • Lee MJ, Kim MY, Mo JS, et al. Indirubin-3′-monoxime, a derivative of a Chinese anti-leukemia medicine, inhibits Notch1 signaling. Cancer Lett 2008;265(2):215-25
  • Natarajan C, Bright JJ. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. J Immunol 2002;168(12):6506-13
  • Bharti AC, Donato N, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol 2003;171(7):3863-71
  • Kagialis-Girard S, Mialou V, Chebel A, et al. Inhibition of normal lymphocyte proliferation by Indirubin-3′-monoxime: a multifactorial process. Leuk Lymphoma 2007;48(3):605-15
  • Gonzales AM, Orlando RA. Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes. Nutr Metab (Lond) 2008;5:17
  • Mackenzie GG, Queisser N, Wolfson ML, et al. 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 2008;123(1):56-65
  • Yu CL, Meyer DJ, Campbell GS, et al. Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science 1995;269(5220):81-3
  • Bowman T, Garcia R, Turkson J, Jove R. STATs in oncogenesis. Oncogene 2000;19(21):2474-88
  • Al Zaid Siddiquee K, Turkson J. STAT3 as a target for inducing apoptosis in solid and hematological tumors. Cell Res 2008;18(2):254-67
  • Fletcher S, Turkson J, Gunning PT. Molecular approaches towards the inhibition of the signal transducer and activator of transcription 3 (Stat3) protein. ChemMedChem 2008;3(8):1159-68
  • Wang S, Yang D, Lippman ME. Targeting Bcl-2 and Bcl-XL with nonpeptidic small-molecule antagonists. Semin Oncol 2003;30(5 Suppl 16):133-42
  • Mohammad RM, Goustin AS, Aboukameel A, et al. Preclinical studies of TW-37, a new nonpeptidic small-molecule inhibitor of Bcl-2, in diffuse large cell lymphoma xenograft model reveal drug action on both Bcl-2 and Mcl-1. Clin Cancer Res 2007;13(7):2226-35
  • Mohammad RM, Wang S, Aboukameel A, et al. Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-X(L) [(-)-gossypol] against diffuse large cell lymphoma. Mol Cancer Ther 2005;4(1):13-21

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