期刊论文

【摘要】

Activation of nuclear factor-kappa B (NF- κB) as a mechanism of host defense against infection and stress is the central mediator of inflammatory responses. A normal (acute) inflammatory response is activated on urgent basis and is auto-regulated. Chronic inflammation that results due to failure in the regulatory mechanism, however, is largely considered as a critical determinant in the initiation and progression of various forms of cancer. Mechanistically, NF- κB favors this process by inducing various genes responsible for cell survival, proliferation, migration, invasion while at the same time antagonizing growth regulators including tumor suppressor p53. It has been shown by various independent investigations that a down regulation of NF- κB activity directly, or indirectly through the activation of the p53 pathway reduces tumor growth substantially. Therefore, there is a huge effort driven by many laboratories to understand the NF- κB signaling pathways to intervene the function of this crucial player in inflammation and tumorigenesis in order to find an effective inhibitor directly, or through the p53 tumor suppressor. We discuss here on the role of NF- κB in chronic inflammation and cancer, highlighting mutual antagonism between NF- κB and p53 pathways in the process. We also discuss prospective pharmacological modulators of these two pathways, including those that were already tested to affect this mutual antagonism.

【授权许可】

2014 Pal et al.; licensee BioMed Central Ltd.

【预览】

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【参考文献】

[1]Stein CJ, Colditz GA: Modifiable risk factors for cancer. Br J Cancer 2004, 90:299-303.
[2]Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB: Cancer is a preventable disease that requires major lifestyle changes. Pharm Res 2008, 25:2097-2116.
[3]Rossi AG, Sawatzky DA: The Resolution of Inflammation. Birkhauser: Basel; 2008.
[4]Balkwill F, Mantovani A: Inflammation and cancer: back to Virchow? Lancet 2001, 357:539-545.
[5]Coussens LM, Werb Z: Inflammation and cancer. Nature 2002, 420:860-867.
[6]Philip M, Rowley DA, Schreiber H: Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol 2004, 14:433-439.
[7]Beekhuizen H, van Furth R: Monocyte adherence to human vascular endothelium. J Leukoc Biol 1993, 54:363-378.
[8]Kulidjian AA, Inman R, Issekutz TB: Rodent models of lymphocyte migration. Semin Immunol 1999, 11:85-93.
[9]van Gils JM, Zwaginga JJ, Hordijk PL: Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases. J Leukoc Biol 2009, 85:195-204.
[10]Eming SA, Krieg T, Davidson JM: Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 2007, 127:514-525.
[11]Weiss SJ: Tissue destruction by neutrophils. N Engl J Med 1989, 320:365-376.
[12]Balkwill F, Coussens LM: Cancer: an inflammatory link. Nature 2004, 431:405-406.
[13]Sato Y, Ohshima T, Kondo T: Regulatory role of endogenous interleukin-10 in cutaneous inflammatory response of murine wound healing. Biochem Biophys Res Commun 1999, 265:194-199.
[14]Erdman SE, Poutahidis T: Roles for inflammation and regulatory T cells in colon cancer. Toxicol Pathol 2010, 38:76-87.
[15]Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W: Interleukin-10-deficient mice develop chronic enterocolitis. Cell 1993, 75:263-274.
[16]Ho L, Davis RE, Conne B, Chappuis R, Berczy M, Mhawech P, Staudt LM, Schwaller J: MALT1 and the API2-MALT1 fusion act between CD40 and IKK and confer NF-kappa B-dependent proliferative advantage and resistance against FAS-induced cell death in B cells. Blood 2005, 105:2891-2899.
[17]Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A: Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001, 19:683-765.
[18]Rizzo A, Pallone F, Monteleone G, Fantini MC: Intestinal inflammation and colorectal cancer: a double-edged sword? World J Gastroenterol 2011, 17:3092-3100.
[19]Schottelius AJ, Mayo MW, Sartor RB, Baldwin AS Jr: Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding. J Biol Chem 1999, 274:31868-31874.
[20]Mantovani A: Molecular pathways linking inflammation and cancer. Curr Mol Med 2010, 10:369-373.
[21]Harhaj EW, Dixit VM: Deubiquitinases in the regulation of NF-kappaB signaling. Cell Res 2012, 21:22-39.
[22]de Visser KE, Eichten A, Coussens LM: Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 2006, 6:24-37.
[23]Lin WW, Karin M: A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007, 117:1175-1183.
[24]Kuper H, Adami HO, Trichopoulos D: Infections as a major preventable cause of human cancer. J Intern Med 2000, 248:171-183.
[25]Sunami Y, Wirth T: Intestinal carcinogenesis: IKK can go all the way. J Clin Invest 2011, 121:2551-2553.
[26]Mossman BT, Lounsbury KM, Reddy SP: Oxidants and signaling by mitogen-activated protein kinases in lung epithelium. Am J Respir Cell Mol Biol 2006, 34:666-669.
[27]Vaid M, Katiyar SK: Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.) (Review). Int J Oncol 2010, 36:1053-1060.
[28]Schutte K, Bornschein J, Malfertheiner P: Hepatocellular carcinoma–epidemiological trends and risk factors. Dig Dis 2009, 27:80-92.
[29]Stauffer JK, Scarzello AJ, Jiang Q, Wiltrout RH: Chronic inflammation, immune escape and oncogenesis in the liver: a unique neighborhood for novel intersections. Hepatology 2012, 56(4):1567-1574.
[30]Loffeld RJ, Willems I, Flendrig JA, Arends JW: Helicobacter pylori and gastric carcinoma. Histopathology 1990, 17:537-541.
[31]Stolte M: Helicobacter pylori gastritis and gastric MALT-lymphoma. Lancet 1992, 339:745-746.
[32]Ernst PB, Gold BD: The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol 2000, 54:615-640.
[33]Shacter E, Weitzman SA: Chronic inflammation and cancer. Oncology (Williston Park) 2002, 16:217-226, 229; discussion 230–212.
[34]Nicholson A, Jankowski J: Acid reflux and oesophageal cancer. Recent Results Cancer Res 2011, 185:65-82.
[35]Gryseels B: Schistosomiasis. Infect Dis Clin North Am 2012, 26:383-397.
[36]Parkin DM: The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006, 118:3030-3044.
[37]King CH: Parasites and poverty: the case of schistosomiasis. Acta Trop 2010, 113:95-104.
[38]Schwartz DA: Helminths in the induction of cancer: Opisthorchis viverrini, Clonorchis sinensis and cholangiocarcinoma. Trop Geogr Med 1980, 32:95-100.
[39]Abraham C, Medzhitov R: Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology 2011, 140:1729-1737.
[40]Clapper ML, Gary MA, Coudry RA, Litwin S, Chang WC, Devarajan K, Lubet RA, Cooper HS: 5-aminosalicylic acid inhibits colitis-associated colorectal dysplasias in the mouse model of azoxymethane/dextran sulfate sodium-induced colitis. Inflamm Bowel Dis 2008, 14:1341-1347.
[41]de Martel C, Franceschi S: Infections and cancer: established associations and new hypotheses. Crit Rev Oncol Hematol 2009, 70:183-194.
[42]Grewal P, Viswanathen VA: Liver cancer and alcohol. Clin Liver Dis 2012, 16:839-850.
[43]Rook GA, Dalgleish A: Infection, immunoregulation, and cancer. Immunol Rev 240:141-159.
[44]Wang HJ, Gao B, Zakhari S, Nagy LE: Inflammation in alcoholic liver disease. Annu Rev Nutr 2012, 32:343-368.
[45]Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM: The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990, 63:1129-1136.
[46]James JA, Kaufman KM, Farris AD, Taylor-Albert E, Lehman TJ, Harley JB: An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus. J Clin Invest 1997, 100:3019-3026.
[47]Kutok JL, Wang F: Spectrum of Epstein-Barr virus-associated diseases. Annu Rev Pathol 2006, 1:375-404.
[48]Mackenzie I, Rous P: The experimental disclosure of latent neoplastic changes in tarred skin. J Exp Med 1941, 73:391-416.
[49]Balkwill F, Charles KA, Mantovani A: Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 2005, 7:211-217.
[50]Velicer CM, Heckbert SR, Lampe JW, Potter JD, Robertson CA, Taplin SH: Antibiotic use in relation to the risk of breast cancer. JAMA 2004, 291:827-835.
[51]Attur MG, Patel RN, Patel PD, Abramson SB, Amin AR: Tetracycline up-regulates COX-2 expression and prostaglandin E2 production independent of its effect on nitric oxide. J Immunol 1999, 162:3160-3167.
[52]Enzler T, Gillessen S, Manis JP, Ferguson D, Fleming J, Alt FW, Mihm M, Dranoff G: Deficiencies of GM-CSF and interferon gamma link inflammation and cancer. J Exp Med 2003, 197:1213-1219.
[53]Ghosh S, Karin M: Missing pieces in the NF-kappaB puzzle. Cell 2002, 109 Suppl:S81-S96.
[54]Ghosh S, Hayden MS: Celebrating 25 years of NF-kappaB research. Immunol Rev 2012, 246:5-13.
[55]Sen R, Baltimore D: Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell 1986, 47:921-928.
[56]Karin M, Ben-Neriah Y: Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol 2000, 18:621-663.
[57]Vallabhapurapu S, Karin M: Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 2009, 27:693-733.
[58]Karin M, Yamamoto Y, Wang QM: The IKK NF-kappa B system: a treasure trove for drug development. Nat Rev Drug Discov 2004, 3:17-26.
[59]Zhong H, May MJ, Jimi E, Ghosh S: The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1. Mol Cell 2002, 9:625-636.
[60]Cha-Molstad H, Agrawal A, Zhang D, Samols D, Kushner I: The Rel family member P50 mediates cytokine-induced C-reactive protein expression by a novel mechanism. J Immunol 2000, 165:4592-4597.
[61]Perkins ND: Oncogenes, tumor suppressors and p52 NF-kappaB. Oncogene 2003, 22:7553-7556.
[62]Akira S: Pathogen recognition by innate immunity and its signaling. Proc Jpn Acad Ser B Phys Biol Sci 2009, 85:143-156.
[63]Medzhitov R: Toll-like receptors and innate immunity. Nat Rev Immunol 2001, 1:135-145.
[64]Girardin SE, Tournebize R, Mavris M, Page AL, Li X, Stark GR, Bertin J, DiStefano PS, Yaniv M, Sansonetti PJ, Philpott DJ: CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri. EMBO Rep 2001, 2:736-742.
[65]Newton K, Dixit VM: Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol 2012, 4:1-19.
[66]Philpott DJ, Yamaoka S, Israel A, Sansonetti PJ: Invasive Shigella flexneri activates NF-kappa B through a lipopolysaccharide-dependent innate intracellular response and leads to IL-8 expression in epithelial cells. J Immunol 2000, 165:903-914.
[67]Robertson SJ, Girardin SE: Nod-like receptors in intestinal host defense: controlling pathogens, the microbiota, or both? Curr Opin Gastroenterol 2012, 29:15-22.
[68]Barnich N, Aguirre JE, Reinecker HC, Xavier R, Podolsky DK: Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-{kappa}B activation in muramyl dipeptide recognition. J Cell Biol 2005, 170:21-26.
[69]Fritz JH, Ferrero RL, Philpott DJ, Girardin SE: Nod-like proteins in immunity, inflammation and disease. Nat Immunol 2006, 7:1250-1257.
[70]Sancho D, Reis ESC: Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol 2012, 30:491-529.
[71]Klesney-Tait J, Turnbull IR, Colonna M: The TREM receptor family and signal integration. Nat Immunol 2006, 7:1266-1273.
[72]Arts RJ, Joosten LA, van der Meer JW, Netea MG: TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors. J Leukoc Biol 2012, 93:209-215.
[73]Bouchon A, Dietrich J, Colonna M: Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 2000, 164:4991-4995.
[74]Ford JW, McVicar DW: TREM and TREM-like receptors in inflammation and disease. Curr Opin Immunol 2009, 21:38-46.
[75]Israel A: The IKK complex, a central regulator of NF-kappaB activation. Cold Spring Harb Perspect Biol 2010, 2:a.000158.
[76]Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K: The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 1999, 398:252-256.
[77]Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ: TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 2001, 412:346-351.
[78]Takaesu G, Surabhi RM, Park KJ, Ninomiya-Tsuji J, Matsumoto K, Gaynor RB: TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway. J Mol Biol 2003, 326:105-115.
[79]Irie T, Muta T, Takeshige K: TAK1 mediates an activation signal from toll-like receptor(s) to nuclear factor-kappaB in lipopolysaccharide-stimulated macrophages. FEBS Lett 2000, 467:160-164.
[80]Huang Q, Yang J, Lin Y, Walker C, Cheng J, Liu ZG, Su B: Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3. Nat Immunol 2004, 5:98-103.
[81]Yang J, Lin Y, Guo Z, Cheng J, Huang J, Deng L, Liao W, Chen Z, Liu Z, Su B: The essential role of MEKK3 in TNF-induced NF-kappaB activation. Nat Immunol 2001, 2:620-624.
[82]Delhase M, Hayakawa M, Chen Y, Karin M: Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science 1999, 284:309-313.
[83]Dejardin E, Droin NM, Delhase M, Haas E, Cao Y, Makris C, Li ZW, Karin M, Ware CF, Green DR: The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity 2002, 17:525-535.
[84]Senftleben U, Cao Y, Xiao G, Greten FR, Krähn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M: Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 2001, 293:1495-1499.
[85]Sil AK, Maeda S, Sano Y, Roop DR, Karin M: IkappaB kinase-alpha acts in the epidermis to control skeletal and craniofacial morphogenesis. Nature 2004, 428:660-664.
[86]Novack DV, Yin L, Hagen-Stapleton A, Schreiber RD, Goeddel DV, Ross FP, Teitelbaum SL: The IkappaB function of NF-kappaB2 p100 controls stimulated osteoclastogenesis. J Exp Med 2003, 198:771-781.
[87]DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M: A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature 1997, 388:548-554.
[88]Rothwarf DM, Zandi E, Natoli G, Karin M: IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature 1998, 395:297-300.
[89]Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M: The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell 1997, 91:243-252.
[90]Liu F, Xia Y, Parker AS, Verma IM: IKK biology. Immunol Rev 2012, 246:239-253.
[91]Chen Z, Hagler J, Palombella VJ, Melandri F, Scherer D, Ballard D, Maniatis T: Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev 1995, 9:1586-1597.
[92]Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A, Rao A: IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science 1997, 278:860-866.
[93]Kanarek N, Ben-Neriah Y: Regulation of NF-kappaB by ubiquitination and degradation of the IkappaBs. Immunol Rev 2012, 246:77-94.
[94]Yaron A, Gonen H, Alkalay I, Hatzubai A, Jung S, Beyth S, Mercurio F, Manning AM, Ciechanover A, Ben-Neriah Y: Inhibition of NF-kappa-B cellular function via specific targeting of the I-kappa-B-ubiquitin ligase. EMBO J 1997, 16:6486-6494.
[95]Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning AM, Andersen JS, Mann M, Mercurio F, Ben-Neriah Y: Identification of the receptor component of the IkappaBalpha-ubiquitin ligase. Nature 1998, 396:590-594.
[96]Ghosh G, Wang VY, Huang DB, Fusco A: NF-kappaB regulation: lessons from structures. Immunol Rev 2012, 246:36-58.
[97]Diaz-Meco MT, Moscat J: The atypical PKCs in inflammation: NF-kappaB and beyond. Immunol Rev 2012, 246:154-167.
[98]Ghosh S, Gifford AM, Riviere LR, Tempst P, Nolan GP, Baltimore D: Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal. Cell 1990, 62:1019-1029.
[99]Gilmore TD: NF-kappa B, KBF1, dorsal, and related matters. Cell 1990, 62:841-843.
[100]Karin M, Greten FR: NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 2005, 5:749-759.
[101]Aggarwal BB, Gehlot P: Inflammation and cancer: how friendly is the relationship for cancer patients? Curr Opin Pharmacol 2009, 9:351-369.
[102]Staudt LM: Oncogenic activation of NF-kappaB. Cold Spring Harb Perspect Biol 2010, 2:a.000109.
[103]Gasparian AV, Burkhart CA, Purmal AA, Brodsky L, Pal M, Saranadasa M, Bosykh DA, Commane M, Guryanova OA, Pal S, Safina A, Sviridov S, Koman IE, Veith J, Komar AA, Gudkov AV, Gurova KV: Curaxins: anticancer compounds that simultaneously suppress NF-kappaB and activate p53 by targeting FACT. Sci Transl Med 2011, 3:95ra74.
[104]Gurova KV, Hill JE, Guo C, Prokvolit A, Burdelya LG, Samoylova E, Khodyakova AV, Ganapathi R, Ganapathi M, Tararova ND, Bosykh D, Lvovskiy D, Webb TR, Stark GR, Gudkov AV: Small molecules that reactivate p53 in renal cell carcinoma reveal a NF-kappaB-dependent mechanism of p53 suppression in tumors. Proc Natl Acad Sci U S A 2005, 102:17448-17453.
[105]Vlantis K, Wullaert A, Sasaki Y, Schmidt-Supprian M, Rajewsky K, Roskams T, Pasparakis M: Constitutive IKK2 activation in intestinal epithelial cells induces intestinal tumors in mice. J Clin Invest 2011, 121:2781-2793.
[106]Natarajan V, Komarov AP, Ippolito T, Bonneau K, Chenchik AA, Gudkov AV: Peptides genetically selected for NF-kappaB activation cooperate with oncogene Ras and model carcinogenic role of inflammation. Proc Natl Acad Sci U S A 2014, 111:E474-E483.
[107]Sun J, Wiklund F, Hsu FC, Bälter K, Zheng SL, Johansson JE, Chang B, Liu W, Li T, Turner AR, Li L, Li G, Adami HO, Isaacs WB, Xu J, Grönberg H: Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the toll-like receptor 6-1-10 gene cluster increase prostate cancer risk. Cancer Epidemiol Biomarkers Prev 2006, 15:480-485.
[108]So EY, Ouchi T: The application of Toll like receptors for cancer therapy. Int J Biol Sci 2010, 6:675-681.
[109]Yu L, Chen S: Toll-like receptors expressed in tumor cells: targets for therapy. Cancer Immunol Immunother 2008, 57:1271-1278.
[110]Fukata M, Chen A, Vamadevan AS, Cohen J, Breglio K, Krishnareddy S, Hsu D, Xu R, Harpaz N, Dannenberg AJ, Subbaramaiah K, Cooper HS, Itzkowitz SH, Abreu MT: Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology 2007, 133:1869-1881.
[111]Wolska A, Lech-Maranda E, Robak T: Toll-like receptors and their role in carcinogenesis and anti-tumor treatment. Cell Mol Biol Lett 2009, 14:248-272.
[112]Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, et al.: Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 2008, 40:955-962.
[113]Hugot JP: [Role of NOD2 gene in Crohn’s disease]. Gastroenterol Clin Biol 2002, 26:13-15.
[114]Xavier RJ, Podolsky DK: Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007, 448:427-434.
[115]Eckmann L, Karin M: NOD2 and Crohn’s disease: loss or gain of function? Immunity 2005, 22:661-667.
[116]Sehouli J, Mustea A, Konsgen D, Katsares I, Lichtenegger W: Polymorphism of IL-1 receptor antagonist gene: role in cancer. Anticancer Res 2002, 22:3421-3424.
[117]Troost E, Hold GL, Smith MG, Chow WH, Rabkin CS, McColl KE, El-Omar EM: The role of interleukin-1beta and other potential genetic markers as indicators of gastric cancer risk. Can J Gastroenterol 2003, 17 Suppl B:8B-12B.
[118]Apte RN, Dotan S, Elkabets M, White MR, Reich E, Carmi Y, Song X, Dvozkin T, Krelin Y, Voronov E: The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions. Cancer Metastasis Rev 2006, 25:387-408.
[119]Lewis AM, Varghese S, Xu H, Alexander HR: Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. J Transl Med 2006, 4:48.
[120]Lawrence T: The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol 2009, 1:a.001651.
[121]Prasad S, Ravindran J, Aggarwal BB: NF-kappaB and cancer: how intimate is this relationship. Mol Cell Biochem 2010, 336:25-37.
[122]Fodde R, Smits R, Clevers H: APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer 2001, 1:55-67.
[123]Ahmad R, Raina D, Trivedi V, Ren J, Rajabi H, Kharbanda S, Kufe D: MUC1 oncoprotein activates the IkappaB kinase beta complex and constitutive NF-kappaB signalling. Nat Cell Biol 2007, 9:1419-1427.
[124]Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, Dave SS, Zhao H, Xu W, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Chan WC, Staudt LM: Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 2008, 319:1676-1679.
[125]Yamaoka S, Inoue H, Sakurai M, Sugiyama T, Hazama M, Yamada T, Hatanaka M: Constitutive activation of NF-kappa B is essential for transformation of rat fibroblasts by the human T-cell leukemia virus type I Tax protein. EMBO J 1996, 15:873-887.
[126]Wood KM, Roff M, Hay RT: Defective IkappaBalpha in Hodgkin cell lines with constitutively active NF-kappaB. Oncogene 1998, 16:2131-2139.
[127]Mehta K: Biological and therapeutic significance of tissue transglutaminase in pancreatic cancer. Amino Acids 2009, 36:709-716.
[128]Mann AP, Verma A, Sethi G, Manavathi B, Wang H, Fok JY, Kunnumakkara AB, Kumar R, Aggarwal BB, Mehta K: Overexpression of tissue transglutaminase leads to constitutive activation of nuclear factor-kappaB in cancer cells: delineation of a novel pathway. Cancer Res 2006, 66:8788-8795.
[129]Gudkov AV, Gurova KV, Komarova EA: Inflammation and p53: a tale of two stresses. Genes Cancer 2011, 2:503-516.
[130]Vucic D, Dixit VM, Wertz IE: Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death. Nat Rev Mol Cell Biol 2011, 12:439-452.
[131]Huang WC, Ju TK, Hung MC, Chen CC: Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB. Mol Cell 2007, 26:75-87.
[132]Mayo MW, Madrid LV, Westerheide SD, Jones DR, Yuan XJ, Baldwin ASJr., Whang YE: PTEN blocks tumor necrosis factor-induced NF-kappa B-dependent transcription by inhibiting the transactivation potential of the p65 subunit. J Biol Chem 2002, 277:11116-11125.
[133]Perkins ND: The diverse and complex roles of NF-kappaB subunits in cancer. Nat Rev Cancer 2012, 12:121-132.
[134]Rocha S, Campbell KJ, Perkins ND: p53- and Mdm2-independent repression of NF-kappa B transactivation by the ARF tumor suppressor. Mol Cell 2003, 12:15-25.
[135]Wolff B, Naumann M: INK4 cell cycle inhibitors direct transcriptional inactivation of NF-kappaB. Oncogene 1999, 18:2663-2666.
[136]Kashima L, Toyota M, Mita H, Suzuki H, Idogawa M, Ogi K, Sasaki Y, Tokino T: CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-kappaB. Oncogene 2009, 28:2643-2653.
[137]Rattan R, Narita K, Chien J, Maguire JL, Shridhar R, Giri S, Shridhar V: TCEAL7, a putative tumor suppressor gene, negatively regulates NF-kappaB pathway. Oncogene 2010, 29:1362-1373.
[138]Wang J, An H, Mayo MW, Baldwin AS, Yarbrough WG: LZAP, a putative tumor suppressor, selectively inhibits NF-kappaB. Cancer Cell 2007, 12:239-251.
[139]Dell’Orso S, Fontemaggi G, Stambolsky P, Goeman F, Voellenkle C, Levrero M, Strano S, Rotter V, Oren M, Blandino G: ChIP-on-chip analysis of in vivo mutant p53 binding to selected gene promoters. OMICS 2011, 15:305-312.
[140]Gudkov AV, Komarova EA: Pathologies associated with the p53 response. Cold Spring Harb Perspect Biol 2010, 2:a.001180.
[141]Murray-Zmijewski F, Slee EA, Lu X: A complex barcode underlies the heterogeneous response of p53 to stress. Nat Rev Mol Cell Biol 2008, 9:702-712.
[142]Ak P, Levine AJ: p53 and NF-kappaB: different strategies for responding to stress lead to a functional antagonism. FASEB J 2010, 24:3643-3652.
[143]Hu W, Feng Z, Levine AJ: The regulation of multiple p53 stress responses is mediated through MDM2. Genes Cancer 2012, 3:199-208.
[144]Huang L, Yan Z, Liao X, Li Y, Yang J, Wang ZG, Zuo Y, Kawai H, Shadfan M, Ganapathy S, Yuan ZM: The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo. Proc Natl Acad Sci U S A 2011, 108:12001-12006.
[145]Pant V, Xiong S, Iwakuma T, Quintas-Cardama A, Lozano G: Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability. Proc Natl Acad Sci U S A 2011, 108:11995-12000.
[146]Wade M, Li YC, Wahl GM: MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer 2013, 13:83-96.
[147]Mayo LD, Turchi JJ, Berberich SJ: Mdm-2 phosphorylation by DNA-dependent protein kinase prevents interaction with p53. Cancer Res 1997, 57:5013-5016.
[148]Zuckerman V, Lenos K, Popowicz GM, Silberman I, Grossman T, Marine JC, Holak TA, Jochemsen AG, Haupt Y: c-Abl phosphorylates Hdmx and regulates its interaction with p53. J Biol Chem 2009, 284:4031-4039.
[149]Thut CJ, Goodrich JA, Tjian R: Repression of p53-mediated transcription by MDM2: a dual mechanism. Genes Dev 1997, 11:1974-1986.
[150]Meek DW, Hupp TR: The regulation of MDM2 by multisite phosphorylation–opportunities for molecular-based intervention to target tumours? Semin Cancer Biol 2010, 20:19-28.
[151]Lopez-Pajares V, Kim MM, Yuan ZM: Phosphorylation of MDMX mediated by Akt leads to stabilization and induces 14-3-3 binding. J Biol Chem 2008, 283:13707-13713.
[152]Mayo LD, Donner DB: A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci U S A 2001, 98:11598-11603.
[153]Goh AM, Lim CY, Chiam PC, Li L, Mann MB, Mann KM, Menendez S, Lane DP: Using targeted transgenic reporter mice to study promoter-specific p53 transcriptional activity. Proc Natl Acad Sci U S A 2012, 109:1685-1690.
[154]Toledo F, Wahl GM: Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 2006, 6:909-923.
[155]Fei P, Bernhard EJ, El-Deiry WS: Tissue-specific induction of p53 targets in vivo. Cancer Res 2002, 62:7316-7327.
[156]Goh AM, Lane DP: How p53 wields the scales of fate: arrest or death? Transcription 2012, 3:240-244.
[157]Khoo KH, Verma CS, Lane DP: Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov 2014, 13:217-236.
[158]el-Deiry WS: Regulation of p53 downstream genes. Semin Cancer Biol 1998, 8:345-357.
[159]el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B: Definition of a consensus binding site for p53. Nat Genet 1992, 1:45-49.
[160]Piwnica-Worms H: Cell cycle. Fools Rush Nature 1999, 401:535, 537.
[161]St Clair S, Giono L, Varmeh-Ziaie S, Resnick-Silverman L, Liu WJ, Padi A, Dastidar J, DaCosta A, Mattia M, Manfredi JJ: DNA damage-induced downregulation of Cdc25C is mediated by p53 via two independent mechanisms: one involves direct binding to the cdc25C promoter. Mol Cell 2004, 16:725-736.
[162]Shaw P, Bovey R, Tardy S, Sahli R, Sordat B, Costa J: Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc Natl Acad Sci U S A 1992, 89:4495-4499.
[163]Kortlever RM, Higgins PJ, Bernards R: Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat Cell Biol 2006, 8:877-884.
[164]Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M: Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 1991, 352:345-347.
[165]Crighton D, Wilkinson S, O’Prey J, Syed N, Smith P, Harrison PR, Gasco M, Garrone O, Crook T, Ryan KM: DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 2006, 126:121-134.
[166]Beckerman R, Prives C: Transcriptional regulation by p53. Cold Spring Harb Perspect Biol 2010, 2:a.000935.
[167]Gurova K: New hopes from old drugs: revisiting DNA-binding small molecules as anticancer agents. Future Oncol 2009, 5:1685-1704.
[168]Kashatus D, Cogswell P, Baldwin AS: Expression of the Bcl-3 proto-oncogene suppresses p53 activation. Genes Dev 2006, 20:225-235.
[169]Tergaonkar V, Pando M, Vafa O, Wahl G, Verma I: p53 stabilization is decreased upon NFkappaB activation: a role for NFkappaB in acquisition of resistance to chemotherapy. Cancer Cell 2002, 1:493-503.
[170]Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997, 91:231-241.
[171]Jiang P, Du W, Heese K, Wu M: The Bad guy cooperates with good cop p53: Bad is transcriptionally up-regulated by p53 and forms a Bad/p53 complex at the mitochondria to induce apoptosis. Mol Cell Biol 2006, 26:9071-9082.
[172]Vivanco I, Sawyers CL: The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002, 2:489-501.
[173]Khwaja A: Akt is more than just a Bad kinase. Nature 1999, 401:33-34.
[174]Romashkova JA, Makarov SS: NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 1999, 401:86-90.
[175]Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB: NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 1999, 401:82-85.
[176]Xia Y, Padre RC, De Mendoza TH, Bottero V, Tergaonkar VB, Verma IM: Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP. Proc Natl Acad Sci U S A 2009, 106:2629-2634.
[177]Lowe SW, Sherr CJ: Tumor suppression by Ink4a-Arf: progress and puzzles. Curr Opin Genet Dev 2003, 13:77-83.
[178]Rocha S, Perkins ND: ARF the integrator: linking NF-kappaB, p53 and checkpoint kinases. Cell Cycle 2005, 4:756-759.
[179]Perkins ND: Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 2007, 8:49-62.
[180]Ikeda A, Sun X, Li Y, Zhang Y, Eckner R, Doi TS, Takahashi T, Obata Y, Yoshioka K, Yamamoto K: p300/CBP-dependent and -independent transcriptional interference between NF-kappaB RelA and p53. Biochem Biophys Res Commun 2000, 272:375-379.
[181]Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS, Kelly K: Recruitment of p300/CBP in p53-dependent signal pathways. Cell 1997, 89:1175-1184.
[182]Gerritsen ME, Williams AJ, Neish AS, Moore S, Shi Y, Collins T: CREB-binding protein/p300 are transcriptional coactivators of p65. Proc Natl Acad Sci U S A 1997, 94:2927-2932.
[183]Webster GA, Perkins ND: Transcriptional cross talk between NF-kappaB and p53. Mol Cell Biol 1999, 19:3485-3495.
[184]Tergaonkar V, Perkins ND: p53 and NF-kappaB crosstalk: IKKalpha tips the balance. Mol Cell 2007, 26:158-159.
[185]Kawauchi K, Araki K, Tobiume K, Tanaka N: Activated p53 induces NF-kappaB DNA binding but suppresses its transcriptional activation. Biochem Biophys Res Commun 2008, 372:137-141.
[186]Guo AK, Hou YY, Hirata H, Yamauchi S, Yip AK, Chiam KH, Tanaka N, Sawada Y, Kawauchi K: Loss of p53 enhances NF-kappaB-dependent lamellipodia formation. J Cell Physiol 2014, 229:696-704.
[187]Kawauchi K, Araki K, Tobiume K, Tanaka N: p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation. Nat Cell Biol 2008, 10:611-618.
[188]Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E: The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res 2004, 64:2627-2633.
[189]Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH: TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006, 126:107-120.
[190]Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, Hwang PM: p53 regulates mitochondrial respiration. Science 2006, 312:1650-1653.
[191]Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CAJr., Butel JS, Bradley A: Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992, 356:215-221.
[192]Komarova EA, Krivokrysenko V, Wang K, Neznanov N, Chernov MV, Komarov PG, Brennan ML, Golovkina TV, Rokhlin OW, Kuprash DV, Nedospasov SA, Hazen SL, Feinstein E, Gudkov AV: p53 is a suppressor of inflammatory response in mice. FASEB J 2005, 19:1030-1032.
[193]Appel A: Drugs: more shots on target. Nature 2011, 480:S40-S42.
[194]Gilmore TD, Herscovitch M: Inhibitors of NF-kappaB signaling: 785 and counting. Oncogene 2006, 25:6887-6899.
[195]Alkalay I, Yaron A, Hatzubai A, Orian A, Ciechanover A, Ben-Neriah Y: Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A 1995, 92:10599-10603.
[196]Meister S, Schubert U, Neubert K, Herrmann K, Burger R, Gramatzki M, Hahn S, Schreiber S, Wilhelm S, Herrmann M, Jäck HM, Voll RE: Extensive immunoglobulin production sensitizes myeloma cells for proteasome inhibition. Cancer Res 2007, 67:1783-1792.
[197]Kane RC, Bross PF, Farrell AT, Pazdur R: Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist 2003, 8:508-513.
[198]Kane RC, Farrell AT, Sridhara R, Pazdur R: United States Food and Drug Administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy. Clin Cancer Res 2006, 12:2955-2960.
[199]Ruschak AM, Slassi M, Kay LE, Schimmer AD: Novel proteasome inhibitors to overcome bortezomib resistance. J Natl Cancer Inst 2011, 103:1007-1017.
[200]DiDonato JA, Mercurio F, Karin M: NF-kappaB and the link between inflammation and cancer. Immunol Rev 2012, 246:379-400.
[201]Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH, Sherman NE, Pagano M: S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science 2006, 314:467-471.
[202]Ding Q, He X, Hsu JM, Xia W, Chen CT, Li LY, Lee DF, Liu JC, Zhong Q, Wang X, Hung MC: Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol Cell Biol 2007, 27:4006-4017.
[203]Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello NV, Hershko A, Pagano M, Draetta GF: Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature 2003, 426:87-91.
[204]Kanemori Y, Uto K, Sagata N: Beta-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases. Proc Natl Acad Sci U S A 2005, 102:6279-6284.
[205]Fuchs SY, Chen A, Xiong Y, Pan ZQ, Ronai Z: HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkappaB and beta-catenin. Oncogene 1999, 18:2039-2046.
[206]Kitagawa M, Hatakeyama S, Shirane M, Matsumoto M, Ishida N, Hattori K, Nakamichi I, Kikuchi A, Nakayama K: An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. EMBO J 1999, 18:2401-2410.
[207]Mudduluru G, Medved F, Grobholz R, Jost C, Gruber A, Leupold JH, Post S, Jansen A, Colburn NH, Allgayer H: Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer. Cancer 2007, 110:1697-1707.
[208]Nakajima H, Fujiwara H, Furuichi Y, Tanaka K, Shimbara N: A novel small-molecule inhibitor of NF-kappaB signaling. Biochem Biophys Res Commun 2008, 368:1007-1013.
[209]Fiedler MA, Wernke-Dollries K, Stark JM: Inhibition of TNF-alpha-induced NF-kappaB activation and IL-8 release in A549 cells with the proteasome inhibitor MG-132. Am J Respir Cell Mol Biol 1998, 9:259-268.
[210]Burke JR, Pattoli MA, Gregor KR, Brassil PJ, MacMaster JF, McIntyre KW, Yang X, Iotzova VS, Clarke W, Strnad J, Qiu Y, Zusi FC: BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. J Biol Chem 2003, 278:1450-1456.
[211]Murata T, Shimada M, Sakakibara S, Yoshino T, Masuda T, Shintani T, Sato H, Koriyama Y, Fukushima K, Nunami N, Yamauchi M, Fuchikami K, Komura H, Watanabe A, Ziegelbauer KB, Bacon KB, Lowinger TB: Synthesis and structure-activity relationships of novel IKK-beta inhibitors. Part 3: Orally active anti-inflammatory agents. Bioorg Med Chem Lett 2004, 14:4019-4022.
[212]Lambert C, Li J, Jonscher K, Yang TC, Reigan P, Quintana M, Harvey J, Freed BM: Acrolein inhibits cytokine gene expression by alkylating cysteine and arginine residues in the NF-kappaB1 DNA binding domain. J Biol Chem 2007, 282:19666-19675.
[213]Yore MM, Liby KT, Honda T, Gribble GW, Sporn MB: The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-kappaB activation through direct inhibition of IkappaB kinase beta. Mol Cancer Ther 2006, 5:3232-3239.
[214]Guichard C, Pedruzzi E, Fay M, Marie JC, Braut-Boucher F, Daniel F, Grodet A, Gougerot-Pocidalo MA, Chastre E, Kotelevets L, Lizard G, Vandewalle A, Driss F, Ogier-Denis E: Dihydroxyphenylethanol induces apoptosis by activating serine/threonine protein phosphatase PP2A and promotes the endoplasmic reticulum stress response in human colon carcinoma cells. Carcinogenesis 2006, 27:1812-1827.
[215]Nagashima K, Sasseville VG, Wen D, Bielecki A, Yang H, Simpson C, Grant E, Hepperle M, Harriman G, Jaffee B, Ocain T, Xu Y, Fraser CC: Rapid TNFR1-dependent lymphocyte depletion in vivo with a selective chemical inhibitor of IKKbeta. Blood 2006, 107:4266-4273.
[216]Kishore N, Sommers C, Mathialagan S, Guzova J, Yao M, Hauser S, Huynh K, Bonar S, Mielke C, Albee L, Weier R, Graneto M, Hanau C, Perry T, Tripp CS: A selective IKK-2 inhibitor blocks NF-kappa B-dependent gene expression in interleukin-1 beta-stimulated synovial fibroblasts. J Biol Chem 2003, 278:32861-32871.
[217]Morwick T, Berry A, Brickwood J, Cardozo M, Catron K, DeTuri M, Emeigh J, Homon C, Hrapchak M, Jacober S, Jakes S, Kaplita P, Kelly TA, Ksiazek J, Liuzzi M, Magolda R, Mao C, Marshall D, McNeil D, Prokopowicz A3rd, Sarko C, Scouten E, Sledziona C, Sun S, Watrous J, Wu JP, Cywin CL: Evolution of the thienopyridine class of inhibitors of IkappaB kinase-beta: part I: hit-to-lead strategies. J Med Chem 2006, 49:2898-2908.
[218]Pandey MK, Sandur SK, Sung B, Sethi G, Kunnumakkara AB, Aggarwal BB: Butein, a tetrahydroxychalcone, inhibits nuclear factor (NF)-kappaB and NF-kappaB-regulated gene expression through direct inhibition of IkappaBalpha kinase beta on cysteine 179 residue. J Biol Chem 2007, 282:17340-17350.
[219]Yoon JW, Kang JK, Lee KR, Lee HW, Han JW, Seo DW, Kim YK: beta-Carboline alkaloid suppresses NF-kappaB transcriptional activity through inhibition of IKK signaling pathway. J Toxicol Environ Health A 2005, 68:2005-2017.
[220]Pandey MK, Sung B, Kunnumakkara AB, Sethi G, Chaturvedi MM, Aggarwal BB: Berberine modifies cysteine 179 of IkappaBalpha kinase, suppresses nuclear factor-kappaB-regulated antiapoptotic gene products, and potentiates apoptosis. Cancer Res 2008, 68:5370-5379.
[221]Inayama M, Nishioka Y, Azuma M, Muto S, Aono Y, Makino H, Tani K, Uehara H, Izumi K, Itai A, Sone S: A novel IkappaB kinase-beta inhibitor ameliorates bleomycin-induced pulmonary fibrosis in mice. Am J Respir Crit Care Med 2006, 173:1016-1022.
[222]Castro AC, Dang LC, Soucy F, Grenier L, Mazdiyasni H, Hottelet M, Parent L, Pien C, Palombella V, Adams J: Novel IKK inhibitors: beta-carbolines. Bioorg Med Chem Lett 2003, 13:2419-2422.
[223]Yan SS, Li Y, Wang Y, Shen SS, Gu Y, Wang HB, Qin GW, Yu Q: 17-Acetoxyjolkinolide B irreversibly inhibits IkappaB kinase and induces apoptosis of tumor cells. Mol Cancer Ther 2008, 7:1523-1532.
[224]Mo SJ, Son EW, Lee SR, Lee SM, Shin DH, Pyo S: CML-1 inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in endothelial cells through inhibition of IkBalpha kinase. J Ethnopharmacol 2007, 109:78-86.
[225]Lee JH, Koo TH, Yoon H, Jung HS, Jin HZ, Lee K, Hong YS, Lee JJ: Inhibition of NF-kappa B activation through targeting I kappa B kinase by celastrol, a quinone methide triterpenoid. Biochem Pharmacol 2006, 72:1311-1321.
[226]Shin HM, Lee YR, Chang YS, Lee JY, Kim BH, Min KR, Kim Y: Suppression of interleukin-6 production in macrophages by furonaphthoquinone NFD-37. Int Immunopharmacol 2006, 6:916-923.
[227]Yadav VR, Prasad S, Gupta SC, Sung B, Phatak SS, Zhang S, Aggarwal BB: 3-Formylchromone interacts with cysteine 38 in p65 protein and with cysteine 179 in IkappaBalpha kinase, leading to down-regulation of nuclear factor-kappaB (NF-kappaB)-regulated gene products and sensitization of tumor cells. J Biol Chem 2011, 287:245-256.
[228]Catley MC, Sukkar MB, Chung KF, Jaffee B, Liao SM, Coyle AJ, Haddad el B, Barnes PJ, Newton R: Validation of the anti-inflammatory properties of small-molecule IkappaB Kinase (IKK)-2 inhibitors by comparison with adenoviral-mediated delivery of dominant-negative IKK1 and IKK2 in human airways smooth muscle. Mol Pharmacol 2006, 70:697-705.
[229]Sethi G, Ahn KS, Sung B, Aggarwal BB: Pinitol targets nuclear factor-kappaB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis. Mol Cancer Ther 2008, 7:1604-1614.
[230]Callister ME, Pinhu L, Catley MC, Westwell AD, Newton R, Leaver SK, Quinlan GJ, Evans TW, Griffiths MJ, Burke-Gaffney A: PMX464, a thiol-reactive quinol and putative thioredoxin inhibitor, inhibits NF-kappaB-dependent proinflammatory activation of alveolar epithelial cells. Br J Pharmacol 2008, 155:661-672.
[231]Kuefer R, Genze F, Zugmaier W, Hautmann RE, Rinnab L, Gschwend JE, Angelmeier M, Estrada A, Buechele B: Antagonistic effects of sodium butyrate and N-(4-hydroxyphenyl)-retinamide on prostate cancer. Neoplasia 2007, 9:246-253.
[232]de-Blanco EJ, Pandit B, Hu Z, Shi J, Lewis A, Li PK: Inhibitors of NF-kappaB derived from thalidomide. Bioorg Med Chem Lett 2007, 17:6031-6035.
[233]Huang X, Chen Y, Zhang H, Ma Q, Zhang YW, Xu H: Salubrinal attenuates beta-amyloid-induced neuronal death and microglial activation by inhibition of the NF-kappaB pathway. Neurobiol Aging. 2011 1007, 33:e1009-1017.
[234]Syed DN, Afaq F, Sarfaraz S, Khan N, Kedlaya R, Setaluri V, Mukhtar H: Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation. Toxicol Appl Pharmacol 2008, 231:52-60.
[235]Jagielska J, Salguero G, Schieffer B, Bavendiek U: Digitoxin elicits anti-inflammatory and vasoprotective properties in endothelial cells: therapeutic implications for the treatment of atherosclerosis? Atherosclerosis 2009, 206:390-396.
[236]Xu J, Itoh Y, Hayashi H, Takii T, Miyazawa K, Onozaki K: Dihydrotestosterone inhibits interleukin-1alpha or tumor necrosis factor alpha-induced proinflammatory cytokine production via androgen receptor-dependent inhibition of nuclear factor-kappaB activation in rheumatoid fibroblast-like synovial cell line. Biol Pharm Bull 2011, 34:1724-1730.
[237]Kim HK, Park HR, Lee JS, Chung TS, Chung HY, Chung J: Down-regulation of iNOS and TNF-alpha expression by kaempferol via NF-kappaB inactivation in aged rat gingival tissues. Biogerontology 2007, 8:399-408.
[238]Chiu FL, Lin JK: Tomatidine inhibits iNOS and COX-2 through suppression of NF-kappaB and JNK pathways in LPS-stimulated mouse macrophages. FEBS Lett 2008, 582:2407-2412.
[239]Sarkar D, Saha P, Gamre S, Bhattacharjee S, Hariharan C, Ganguly S, Sen R, Mandal G, Chattopadhyay S, Majumdar S, Chatterjee M: Anti-inflammatory effect of allylpyrocatechol in LPS-induced macrophages is mediated by suppression of iNOS and COX-2 via the NF-kappaB pathway. Int Immunopharmacol 2008, 8:1264-1271.
[240]Hwang J, Zheng LT, Ock J, Lee MG, Kim SH, Lee HW, Lee WH, Park HC, Suk K: Inhibition of glial inflammatory activation and neurotoxicity by tricyclic antidepressants. Neuropharmacology 2008, 55:826-834.
[241]Rajapakse N, Kim MM, Mendis E, Kim SK: Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated RAW264.7 cells by carboxybutyrylated glucosamine takes place via down-regulation of mitogen-activated protein kinase-mediated nuclear factor-kappaB signaling. Immunology 2008, 123:348-357.
[242]Zhu WW, Liu XP, Wu N, Zhao TT, Zhao Y, Zhang J, Shao JH: Beneficial effects of losartan on vascular injury induced by advanced glycosylation end products and their receptors in spontaneous hypertension rats. Mol Cell Biochem 2007, 304:35-43.
[243]Kim HG, Hien TT, Han EH, Hwang YP, Choi JH, Kang KW, Kwon KI, Kim BH, Kim SK, Song GY, Jeong TC, Jeong HG: Metformin inhibits P-glycoprotein expression via the NF-kappaB pathway and CRE transcriptional activity through AMPK activation. Br J Pharmacol 2008, 162:1096-1108.
[244]Boost KA, Leipold T, Scheiermann P, Hoegl S, Sadik CD, Hofstetter C, Zwissler B: Sevoflurane and isoflurane decrease TNF-alpha-induced gene expression in human monocytic THP-1 cells: potential role of intracellular IkappaBalpha regulation. Int J Mol Med 2009, 23:665-671.
[245]Dey A, Wong ET, Cheok CF, Tergaonkar V, Lane DP: R-Roscovitine simultaneously targets both the p53 and NF-kappaB pathways and causes potentiation of apoptosis: implications in cancer therapy. Cell Death Differ 2008, 15:263-273.
[246]Doleckova I, Cesnek M, Dracinsky M, Brynda J, Voller J, Janeba Z, Krystof V: Synthesis and biological evaluation of guanidino analogues of roscovitine. Eur J Med Chem 2013, 62:443-452.
[247]Lu W, Chen L, Peng Y, Chen J: Activation of p53 by roscovitine-mediated suppression of MDM2 expression. Oncogene 2001, 20:3206-3216.
[248]Lew QJ, Chia YL, Chu KL, Lam YT, Gurumurthy M, Xu S, Lam KP, Cheong N, Chao SH: Identification of HEXIM1 as a positive regulator of p53. J Biol Chem 2012, 287:36443-36454.
[249]Peterlin BM, Price DH: Controlling the elongation phase of transcription with P-TEFb. Mol Cell 2006, 23:297-305.
[250]Takada Y, Aggarwal BB: Flavopiridol inhibits NF-kappaB activation induced by various carcinogens and inflammatory agents through inhibition of IkappaBalpha kinase and p65 phosphorylation: abrogation of cyclin D1, cyclooxygenase-2, and matrix metalloprotease-9. J Biol Chem 2004, 279:4750-4759.
[251]Dey A, Wong ET, Bist P, Tergaonkar V, Lane DP: Nutlin-3 inhibits the NFkappaB pathway in a p53-dependent manner: implications in lung cancer therapy. Cell Cycle 2007, 6:2178-2185.
[252]Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA: In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004, 303:844-848.
[253]Anand P, Sung B, Kunnumakkara AB, Rajasekharan KN, Aggarwal BB: Suppression of pro-inflammatory and proliferative pathways by diferuloylmethane (curcumin) and its analogues dibenzoylmethane, dibenzoylpropane, and dibenzylideneacetone: role of Michael acceptors and Michael donors. Biochem Pharmacol 2011, 82:1901-1909.
[254]Gupta SC, Prasad S, Kim JH, Patchva S, Webb LJ, Priyadarsini IK, Aggarwal BB: Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep 2011, 28:1937-1955.
[255]Harikumar KB, Kunnumakkara AB, Ahn KS, Anand P, Krishnan S, Guha S, Aggarwal BB: Modification of the cysteine residues in IkappaBalpha kinase and NF-kappaB (p65) by xanthohumol leads to suppression of NF-kappaB-regulated gene products and potentiation of apoptosis in leukemia cells. Blood 2009, 113:2003-2013.
[256]Shehzad A, Lee YS: Molecular mechanisms of curcumin action: signal transduction. Biofactors 2013, 39:27-36.
[257]Guo C, Gasparian AV, Zhuang Z, Bosykh DA, Komar AA, Gudkov AV, Gurova KV: 9-Aminoacridine-based anticancer drugs target the PI3K/AKT/mTOR, NF-kappaB and p53 pathways. Oncogene 2009, 28:1151-1161.
[258]Manna SK, Bose JS, Gangan V, Raviprakash N, Navaneetha T, Raghavendra PB, Babajan B, Kumar CS, Jain SK: Novel derivative of benzofuran induces cell death mostly by G2/M cell cycle arrest through p53-dependent pathway but partially by inhibition of NF-kappaB. J Biol Chem 2010, 285:22318-22327.
[259]Lu C, Guo Y, Yan J, Luo Z, Luo HB, Yan M, Huang L, Li X: Design, synthesis, and evaluation of multitarget-directed resveratrol derivatives for the treatment of Alzheimer’s disease. J Med Chem 2013, 56:5843-5859.
[260]Michan S, Sinclair D: Sirtuins in mammals: insights into their biological function. Biochem J 2007, 404:1-13.
[261]Saunders LR, Verdin E: Sirtuins: critical regulators at the crossroads between cancer and aging. Oncogene 2007, 26:5489-5504.
[262]Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW: Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004, 23:2369-2380.
[263]Culmsee C, Zhu X, Yu QS, Chan SL, Camandola S, Guo Z, Greig NH, Mattson MP: A synthetic inhibitor of p53 protects neurons against death induced by ischemic and excitotoxic insults, and amyloid beta-peptide. J Neurochem 2001, 77:220-228.
[264]Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, Chernov MV, Gudkov AV: A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 1999, 285:1733-1737.
[265]Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP: Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets 2011, 11:239-253.
[266]Ahn SH, Keogh MC, Buratowski S: Ctk1 promotes dissociation of basal transcription factors from elongating RNA polymerase II. EMBO J 2009, 28:205-212.
[267]Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ: Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood 2007, 110:3281-3290.
[268]Mujtaba T, Dou QP: Advances in the understanding of mechanisms and therapeutic use of bortezomib. Discov Med 2011, 12:471-480.
[269]Chauhan D, Catley L, Li G, Podar K, Hideshima T, Velankar M, Mitsiades C, Mitsiades N, Yasui H, Letai A, Ovaa H, Berkers C, Nicholson B, Chao TH, Neuteboom ST, Richardson P, Palladino MA, Anderson KC: A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell 2005, 8:407-419.
[270]Groll M, Potts BC: Proteasome structure, function, and lessons learned from beta-lactone inhibitors. Curr Top Med Chem 2011, 11:2850-2878.
[271]Obaidat A, Weiss J, Wahlgren B, Manam RR, Macherla VR, McArthur K, Chao TH, Palladino MA, Lloyd GK, Potts BC, Enna SJ, Neuteboom ST, Hagenbuch B: Proteasome regulator marizomib (NPI-0052) exhibits prolonged inhibition, attenuated efflux, and greater cytotoxicity than its reversible analogs. J Pharmacol Exp Ther 2011, 337:479-486.
[272]Potts BC, Albitar MX, Anderson KC, Baritaki S, Berkers C, Bonavida B, Chandra J, Chauhan D, Cusack JCJr, Fenical W, Ghobrial IM, Groll M, Jensen PR, Lam KS, Lloyd GK, McBride W: McConkey: Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets 2011, 11:254-284.
[273]Yang H, Zonder JA, Dou QP: Clinical development of novel proteasome inhibitors for cancer treatment. Expert Opin Investig Drugs 2009, 18:957-971.
[274]Chauhan D, Singh AV, Aujay M, Kirk CJ, Bandi M, Ciccarelli B, Raje N, Richardson P, Anderson KC: A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood 2010, 116:4906-4915.
[275]Dick LR, Fleming PE: Building on bortezomib: second-generation proteasome inhibitors as anti-cancer therapy. Drug Discov Today 2010, 15:243-249.
[276]Kisselev AF, van der Linden WA, Overkleeft HS: Proteasome inhibitors: an expanding army attacking a unique target. Chem Biol 2012, 19:99-115.
[277]Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, Yu J, Yang Y, Hales P, Bruzzese F, Liu J, Blank J, Garcia K, Tsu C, Dick L, Fleming P, Yu L, Manfredi M, Rolfe M, Bolen J: Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res 2010, 70:1970-1980.
[278]Dredge K, Dalgleish AG, Marriott JB: Thalidomide analogs as emerging anti-cancer drugs. Anticancer Drugs 2003, 14:331-335.
[279]Keifer JA, Guttridge DC, Ashburner BP, Baldwin AS Jr: Inhibition of NF-B activity by thalidomide through suppression of IB kinase activity. J Biol Chem 2001, 276:22382-22387.
[280]Majumdar S, Lamothe B, Aggarwal BB: Thalidomide suppresses NF-κB activation induced by TNF and H2O2, but not that activated by ceramide, lipopolysaccharides, or phorbol ester. J Immunol 2002, 168:2644-2651.
[281]Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T, Munshi NC, Treon SP, Anderson KC: Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002, 99:4525-4530.
[282]Gilroy DW, Colville-Nash PR, Willis D, Chivers J, Paul-Clark MJ, Willoughby DA: Inducible cyclooxygenase may have antiinflammatory properties. Nat Med 1999, 5:698-701.
[283]Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK: The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 1998, 391:79-82.
[284]Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro MG: Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 2000, 403:103-108.
[285]Chen J, Zhao M, Rao R, Inoue H, Hao CM: C/EBP{beta} and its binding element are required for NF{kappa}B-induced COX2 expression following hypertonic stress. J Biol Chem 2005, 280:16354-16359.
[286]Okada Y, Voznesensky O, Herschman H, Harrison J, Pilbeam C: Identification of multiple cis-acting elements mediating the induction of prostaglandin G/H synthase-2 by phorbol ester in murine osteoblastic cells. J Cell Biochem 2000, 78:197-209.
[287]Tazawa R, Xu XM, Wu KK, Wang LH: Characterization of the genomic structure, chromosomal location and promoter of human prostaglandin H synthase-2 gene. Biochem Biophys Res Commun 1994, 203:190-199.
[288]Yamamoto Y, Yin MJ, Lin KM, Gaynor RB: Sulindac inhibits activation of the NF-kappaB pathway. J Biol Chem 1999, 274:27307-27314.
[289]Yin MJ, Yamamoto Y, Gaynor RB: The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 1998, 396:77-80.
[290]Pierce JW, Read MA, Ding H, Luscinskas FW, Collins T: Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration. J Immunol 1996, 156:3961-3969.
[291]Wahl C, Liptay S, Adler G, Schmid RM: Sulfasalazine: A potent and specific inhibitor of NF-B. J Clin Invest 1997, 101:1163-1174.
[292]Yan F: Polk DB Aminosalicylic acid inhibits IκB kinase-α phosphorylation of IκBα in mouse intestinal epithelial cells. J Biol Chem 1999, 274:36631-36636.
[293]Egan LJ, Mays DC, Huntoon CJ, Bell MP, Pike MG, Sandborn WJ, Lipsky JJ, McKean DJ: Inhibition of interleukin-1-stimulated NF-κB RelA/p65 phosphorylation by mesalamine is accompanied by decreased transcriptional activity. J Biol Chem 1999, 274:26448-26453.
[294]Yamamoto Y, Verma UN, Prajapati S, Kwak YT, Gaynor RB: Histone H3 phosphorylation by IKK-α is critical for cytokine-induced gene expression. Nature 2003, 423:655-659.
[295]Cao Y, Bonizzi G, Seagroves TN, Greten FR, Johnson R, Schmidt EV, Karin M: IKKα provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development. Cell 2001, 107:763-775.
[296]Anest V, Hanson JL, Cogswell PC, Steinbrecher KA, Strahl BD, Baldwin AS: A nucleosomal function for IκB kinase-αin NF-κB-dependent gene expression. Nature 2003, 423:659-663.
[297]Signal Pharmaceuticals, Inc: Quinazoline analogs and related compounds and methods for treating inflammatory conditions. 1999, WO 199901441.
[298]Leisten JC, Grimshaw CE, Bennett B, Satoh Y, Xu W, O’Leary EC, Firestein GS, Boyle DL, Dreano M, Bhagwat SS, Ramon HK: Identification of a disease modifying IKK2 inhibitor in rat adjuvant arthritis. Inflamm Res 2002, 51(Suppl 2):A25.
[299]Palanki MS, Gayo-Fung LM, Shevlin GI, Erdman P, Sato M, Goldman M, Ransone LJ, Spooner C: Structure–activity relationship studies of ethyl 2-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-4-(trifluoromethyl)pyrimidine-5-carboxylate: an inhibitor of AP-1 and NF-κB mediated gene expression. Bioorg Med Chem Lett 2002, 12:2573-2577.
[300]Adams J, Castro A, Grenier L, Hancock WW, Mazdiyasni H, Palombella V, Ritzeler O, Soucy F: Preparation of substituted carbolines as potential therapeutics in diseases associated with increased IB kinase activity. Aventis Pharma Gmbh 2001.WO 2001068648.
[301]Hideshima T, Chauhan D, Richardson P, Mitsiades C, Mitsiades N, Hayashi T, Munshi N, Dang L, Castro A, Palombella V, Adams J, Anderson KC: NF-κB as a therapeutic target in multiple myeloma. J Biol Chem 2003, 277:16639-16647.
[302]Burke JR, Nadler S, Qiu Y, Townsend RM, Zusi FC: Method of treating inflammatory and immune diseases using 4-amino substituted imidazoquinoxaline, benzopyrazoloquinazoline, benzoimidazoquinoxaline and benzoimidazoquinoline inhibitors of IB kinase (IKK). Bristol-Myers Squibb Co. 2002, WO 2002060386.
[303]Burgess JL, Callahan JF, Wan Z: NF-kB inhibitors. SmithKline Beecham Corp. 2003, WO 2003029242.
[304]Griffiths D, Johnstone C: Preparation of ureido–carboxamido thiophene as inhibitors of IKK2 kinase. AstraZeneca 2003, WO 2003010163.
[305]Baxter A, Brough S, Faull A, Johnstone C, Mcinally T, AstraZeneca: Preparation of thiophenecarboxamides as inhibitors of the enzyme IKK-2. AstraZeneca 2001, WO 2001058890.
[306]Fuchikami K, Ikegami Y, Komura H, Lowinger TB, Masuda T, Murata T, Sakakibara S, Shimada M, Shimazaki M, Shintani T, Umeda M, Yoshida N, Yoshino T, Ziegelbauer KB: Preparation of 2,4-diarylpyridines as IB kinase inhibitors useful as antiinflammatories. Bayer Ag. 2002, WO 2002044153.
[307]Fuchikami K, Hiroshi K, Komura H, Koriyama Y, Lowinger TB, Masuda T, Murata T, Sakakibara S, Sato H, Shimada M, Shintani T, Umeda M, Yoshino T, Ziegelbauer KB: Preparation of hydroxyarylpyridines with IB kinase (IKK) inhibiting activity. Bayer Ag 2002, WO 2002024679.
[308]Murata T, Shimada M, Sakakibara S, Yoshino T, Kadono H, Masuda T, Shimazaki M, Shintani T, Fuchikami K, Sakai K, Inbe H, Takeshita K, Niki T, Umeda M, Bacon KB, Ziegelbauer KB, Lowinger TB: Discovery of novel and selective IKK-β serine-threonine protein kinase inhibitors. Part 1. Bioorg Med Chem Lett 2003, 13:913-918.
[309]Bhagwat SS, Erdman PE, Kois A, Macfarlane KJ, Palanki MSS, Parnes JS, Satoh Y: Preparation of anilinopyrimidines as IKK inhibitors. Signal Pharmaceuticals, Inc 2002, WO 2002046171.
[310]Bacon K, Fuchikami K, Fukushima K, Grosser R, Koriyama Y, Lowinger T, Murata T, Nunami N, Sasaki S, Sato H, Yamauchi M, Yoshino T: Preparation of optically active pyridooxazinones as antiinflammatory agents. Bayer Ag 2003, WO 2003076447.
[311]Madsen MW, Olsen LS: A method using cyanoguanidine compounds for modulating NFkB activity and use for the treatment of cancer. Pharma L 2002, WO 2002094265.
[312]Binderup L, Bramm E, Hamberg KJ, Hjarnaa P-JV: Antitumor drug–cyanoguanidine IKK inhibitor combination. Pharma L 2002, WO 2002094322.
[313]Pierce JW, Schoenleber R, Jesmok G, Best J, Moore SA, Collins T, Gerritsen ME: Novel inhibitors of cytokine-induced IκBα phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J Biol Chem 1997, 272:21096-21103.
[314]Nishimura D, Ishikawa H, Matsumoto K, Shibata H, Motoyoshi Y, Fukuta M, Kawashimo H, Goto T, Taura N, Ichikawa T, Hamasaki K, Nakao K, Umezawa K, Eguchi K: DHMEQ, a novel NF-kappaB inhibitor, induces apoptosis and cell-cycle arrest in human hepatoma cells. Int J Oncol 2006, 29:713-719.
[315]Meng Z, Mitsutake N, Nakashima M, Starenki D, Matsuse M, Takakura S, Namba H, Saenko V, Umezawa K, Ohtsuru A, Yamashita S: DHMEQ, a novel NF-{kappa}B inhibitor, enhances anti-tumor activity of taxanes in anaplastic thyroid cancer cells. Endocrinology 2008, 149:5357-5365.
[316]Kassie F, Melkamu T, Endalew A, Upadhyaya P, Luo X, Hecht SS: Inhibition of lung carcinogenesis and critical cancer-related signaling pathways by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine, indole-3-carbinol and myo-inositol, alone and in combination. Carcinogenesis 2010, 12:1634-1641.
[317]Mackenzie GG, Oteiza PI: Modulation of transcription factor NF-kappaB in Hodgkin’s lymphoma cell lines: effect of (-)-epicatechin. Free Radic Res 2006, 40:1086-1094.
[318]Nicholas C, Batra S, Vargo MA, Voss OH, Gavrilin MA, Wewers MD, Guttridge DC, Grotewold E, Doseff AI: Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-kappaB through the suppression of p65 phosphorylation. J Immunol 2007, 179:7121-7127.
[319]Shukla S, Gupta S: Suppression of constitutive and tumor necrosis factor alpha-induced nuclear factor (NF)-kappaB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells: correlation with down-regulation of NF-kappaB-responsive genes. Clin Cancer Res 2004, 10:3169-3178.
[320]Dai Y, Desano J, Tang W, Meng X, Meng Y, Burstein E, Lawrence TS, Xu L: Natural proteasome inhibitor celastrol suppresses androgen-independent prostate cancer progression by modulating apoptotic proteins and NF-kappaB. PLoS One 2010, 5:e14153.
[321]Wheeler DS, Catravas JD, Odoms K, Denenberg A, Malhotra V, Wong HR: Epigallocatechin-3-gallate, a green tea-derived polyphenol, inhibits IL-1 beta-dependent proinflammatory signal transduction in cultured respiratory epithelial cells. J Nutr 2004, 134:1039-1044.
[322]Kundu JK, Surh YJ: Epigallocatechin gallate inhibits phorbol ester-induced activation of NF-kappa B and CREB in mouse skin: role of p38 MAPK. Ann N Y Acad Sci 2007, 1095:504-512.
[323]Xu L, Zhang L, Bertucci AM, Pope RM, Datta SK: Apigenin, a dietary flavonoid, sensitizes human T cells for activation-induced cell death by inhibiting PKB/Akt and NF-kappaB activation pathway. Immunol Lett 2008, 121:74-83.
[324]Gao X, Deeb D, Liu Y, Gautam S, Dulchavsky SA, Gautam SC: Immunomodulatory activity of xanthohumol: inhibition of T cell proliferation, cell-mediated cytotoxicity and Th1 cytokine production through suppression of NF-kappaB. Immunopharmacol Immunotoxicol 2009, 31:477-484.
[325]Natarajan K, Manna SK, Chaturvedi MM, Aggarwal BB: Protein tyrosine kinase inhibitors block tumor necrosis factor-induced activation of nuclear factor-kappaB, degradation of IkappaBalpha, nuclear translocation of p65, and subsequent gene expression. Arch Biochem Biophys 1998, 352:59-70.
[326]Sarkar FH, Li Y: Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer Metastasis Rev 2002, 21:265-280.
[327]Wang H, Syrovets T, Kess D, Buchele B, Hainzl H, Lunov O, Weiss JM, Scharffetter-Kochanek K, Simmet T: Targeting NF-kappa B with a natural triterpenoid alleviates skin inflammation in a mouse model of psoriasis. J Immunol 2009, 183:4755-4763.
[328]Harikumar KB, Sung B, Pandey MK, Guha S, Krishnan S, Aggarwal BB: Escin, a pentacyclic triterpene, chemosensitizes human tumor cells through inhibition of nuclear factor-kappaB signaling pathway. Mol Pharmacol 2010, 77:818-827.
[329]Harikumar KB, Sung B, Tharakan ST, Pandey MK, Joy B, Guha S, Krishnan S, Aggarwal BB: Sesamin manifests chemopreventive effects through the suppression of NF-kappa B-regulated cell survival, proliferation, invasion, and angiogenic gene products. Mol Cancer Res 2010, 8:751-761.
[330]Jeng KC, Hou RC, Wang JC, Ping LI: Sesamin inhibits lipopolysaccharide-induced cytokine production by suppression of p38 mitogen-activated protein kinase and nuclear factor-kappaB. Immunol Lett 2005, 97:101-106.
[331]Ju W, Wang X, Shi H, Chen W, Belinsky SA, Lin Y: A critical role of luteolin-induced reactive oxygen species in blockage of tumor necrosis factor-activated nuclear factor-kappaB pathway and sensitization of apoptosis in lung cancer cells. Mol Pharmacol 2007, 71:1381-1388.
[332]Kwok BH, Koh B, Ndubuisi MI, Elofsson M, Crews CM: The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol 2001, 8:759-766.
[333]Blackwell TS, Blackwell TR, Holden EP, Christman BW, Christman JW: In vivo antioxidant treatment suppresses nuclear factor-κB activation and neutrophilic lung inflammation. J Immunol 1996, 157:1630-1637.
[334]Bowie AG, O’Neill LA: Vitamin C inhibits NF-κB activation by TNF via the activation of p38 mitogen-activated protein kinase. J Immunol 2000, 165:7180-7188.
[335]Carcamo JM, Pedraza A, Borquez-Ojeda O, Golde DW: Vitamin C suppresses TNFα-induced NF-κB activation by inhibiting IκBα phosphorylation. Biochemistry 2002, 41:12995-13002.
[336]Hayakawa M, Miyashita H, Sakamoto I, Kitagawa M, Tanaka H, Yasuda H, Karin M, Kikugawa K: Evidence that reactive oxygen species do not mediate NF-κB activation. EMBO J 2003, 22:3356-3366.
[337]Rasheed Z, Anbazhagan AN, Akhtar N, Ramamurthy S, Voss FR, Haqqi TM: Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-alpha and matrix metalloproteinase-13 in human chondrocytes. Arthritis Res Ther 2009, 11:R71.
[338]Tabary O, Escotte S, Couetil JP, Hubert D, Dusser D, Puchelle E, Jacquot J: Genistein inhibits constitutive and inducible NFkappaB activation and decreases IL-8 production by human cystic fibrosis bronchial gland cells. Am J Pathol 1999, 155:473-481.
[339]Patel PS, Varney ML, Dave BJ, Singh RK: Regulation of constitutive and induced NF-kappaB activation in malignant melanoma cells by capsaicin modulates interleukin-8 production and cell proliferation. J Interferon Cytokine Res 2002, 22:427-435.
[340]Syrovets T, Gschwend JE, Buchele B, Laumonnier Y, Zugmaier W, Genze F, Simmet T: Inhibition of IkappaB kinase activity by acetyl-boswellic acids promotes apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in vivo. J Biol Chem 2005, 280:6170-6180.
[341]Moon DO, Kim MO, Kang SH, Choi YH, Kim GY: Sulforaphane suppresses TNF-alpha-mediated activation of NF-kappaB and induces apoptosis through activation of reactive oxygen species-dependent caspase-3. Cancer Lett 2009, 274:132-142.
[342]Gupta SC, Kannapan R, Hye Kim J, Rahman GM, Francis SK, Raveendran R, Nair MS, Das J, Aggarwal BB: Bharangin, a diterpenoid quinonemethide, abolishes constitutive and inducible NF-kB activation by modifying p65 on cysteine 38 residue and inhibiting IkBalpha kinase activation, leading to suppression of NF-kB-regulated gene expression and sensitization of tumor cells to chemotherapeutic agents. Mol Pharmacol 2011, 80:769-781.
[343]Tsuboi K, Matsuo Y, Shamoto T, Shibata T, Koide S, Morimoto M, Guha S, Sung B, Aggarwal BB, Takahashi H, Takeyama H: Zerumbone inhibits tumor angiogenesis via NF-kappaB in gastric cancer. Oncol Rep 2014, 31:57-64.
[344]Knight DW: Feverfew: chemistry and biological activity. Nat Prod Rep 1995, 12:271-276.
[345]Wen J, You KR, Lee SY, Song CH, Kim DG: Oxidative stress-mediated apoptosis. The anticancer effect of the sesquiterpene lactone parthenolide. J Biol Chem 2002, 277:38954-38964.
[346]Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, Jordan CT: The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood 2005, 105:4163-4169.
[347]Zhang S, Ong CN, Shen HM: Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells. Cancer Lett 2004, 208:143-153.
[348]Kim JH, Liu L, Lee SO, Kim YT, You KR, Kim DG: Susceptibility of cholangiocarcinoma cells to parthenolide-induced apoptosis. Cancer Res 2005, 65:6312-6320.
[349]Patel NM, Nozaki S, Shortle NH, Bhat-Nakshatri P, Newton TR, Rice S, Gelfanov V, Boswell SH, Goulet RJ Jr, Sledge GW Jr, Nakshatri H: Paclitaxel sensitivity of breast cancer cells with constitutively active NF-κB is enhanced by IκBα super-repressor and parthenolide. Oncogene 2000, 19:4159-4169.
[350]Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB: Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Mol Pharmacol 2006, 69:195-206.
[351]Hussain AR, Ahmed M, Al-Jomah NA, Khan AS, Manogaran P, Sultana M, Abubaker J, Platanias LC, Al-Kuraya KS, Uddin S: Curcumin suppresses constitutive activation of nuclear factor-kappa B and requires functional Bax to induce apoptosis in Burkitt’s lymphoma cell lines. Mol Cancer Ther 2008, 7:3318-3329.
[352]Carroll RE, Benya RV, Turgeon DK, Vareed S, Neuman M, Rodriguez L, Kakarala M, Carpenter PM, McLaren C, Meyskens FL Jr, Brenner DE: Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 2011, 4:354-364.
[353]Saif MW: Is there a role for herbal medicine in the treatment of pancreatic cancer? Highlights from the “44th ASCO Annual Meeting”. Chicago IL, USA. May 30–June 3, 2008. JOP 2008, 9:403-407.
[354]Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar AP, Dou QP: Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res 2008, 68:7283-7292.
[355]Hasima N, Aggarwal BB: Targeting proteasomal pathways by dietary curcumin for cancer prevention and treatment. Curr Med Chem 2014, 21:1583-1594.
[356]Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM: Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997, 275:218-220.
[357]Bhardwaj A, Sethi G, Vadhan-Raj S, Bueso-Ramos C, Takada Y, Gaur U, Nair AS, Shishodia S, Aggarwal BB: 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 2007, 109:2293-2302.
[358]Harikumar KB, Kunnumakkara AB, Sethi G, Diagaradjane P, Anand P, Pandey MK, Gelovani J, Krishnan S, Guha S, Aggarwal BB: Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer 2010, 127:257-268.
[359]Grasberger BL, Lu T, Schubert C, Parks DJ, Carver TE, Koblish HK, Cummings MD, LaFrance LV, Milkiewicz KL, Calvo RR, Maguire D, Lattanze J, Franks CF, Zhao S, Ramachandren K, Bylebyl GR, Zhang M, Manthey CL, Petrella EC, Pantoliano MW, Deckman IC, Spurlino JC, Maroney AC, Tomczuk BE, Molloy CJ, Bone RF: Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells. J Med Chem 2005, 48:909-912.
[360]Allen JG, Bourbeau MP, Wohlhieter GE, Bartberger MD, Michelsen K, Hungate R, Gadwood RC, Gaston RD, Evans B, Mann LW, Matison ME, Schneider S, Huang X, Yu D, Andrews PS, Reichelt A, Long AM, Yakowec P, Yang EY, Lee TA, Oliner JD: Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2 −tumor protein 53 protein −protein interaction. J Med Chem 2009, 52:7044-7053.
[361]Orner BP, Ernst JT, Hamilton AD: Toward proteomimetics: terphenyl derivatives as structural and functional mimics of extended regions of anαhelix. J Am Chem Soc 2001, 123:5382-5383.
[362]Yin H, Lee GI, Park HS, Payne GA, Rodriguez JM, Sebti SM, Hamilton AD: Terphenyl-based helical mimetics that disrupt the p53/HDM2 interaction. Angew Chem Int Ed Engl 2005, 44:2704-2707.
[363]Go ML, Wu X, Liu XL: Chalcones: an update on cytotoxic and chemoprotective properties. Curr Med Chem 2005, 12:483-499.
[364]Stoll R, Renner C, Hansen S, Palme S, Klein C, Belling A, Zeslawski W, Kamionka M, Rehm T, Mühlhahn P, Schumacher R, Hesse F, Kaluza B, Voelter W, Engh RA, Holak TA: Chalcone derivatives antagonize interactions between the human oncoprotein MDM2 and p53. Biochemistry 2001, 40:336-344.
[365]Shangary S, Qin D, McEachern D, Liu M, Miller RS, Qiu S, Nikolovska-Coleska Z, Ding K, Wang G, Chen J, Bernard D, Zhang J, Lu Y, Gu Q, Shah RB, Pienta KJ, Ling X, Kang S, Guo M, Sun Y, Yang D, Wang S: Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proc Natl Acad Sci USA 2008, 105:3933-3938.
[366]Zhao Y, Yu S, Sun W, Liu L, Lu J, McEachern D, Shargary S, Bernard D, Li X, Zhao T, Zou P, Sun D, Wang S: A potent small-molecule inhibitor of the MDM2–p53 interaction (MI888) achieved complete and durable tumor regression in mice. J Med Chem 2013, 56:5553-5561.
[367]Czarna A, Beck B, Srivastava S, Popowicz GM, Wolf S, Huang Y, Bista M, Holak TA, Dömling A: Robust generation of lead compounds for protein–protein interactions by computational and MCR chemistry: 53/Hdm2 antagonists. Angew Chem Int Ed 2010, 49:5352-5356.
[368]Boettcher A, Buschmann N, Furet P, Groell J, Kallen J, Hergovich LJ, Masuya K, Mayr A, Vaupel A: 3imidazolyl-indoles for the treatment of proliferative diseases. 2008, WO Patent2008119741.
[369]Hardcastle IR, Liu J, Valeur E, Watson A, Ahmed SU, Blackburn TJ, Bennaceur K, Clegg W, Drummond C, Endicott JA, Golding BT, Griffin RJ, Gruber J, Haggerty K, Harrington RW, Hutton C, Kemp S, Lu X, McDonnell JM, Newell DR, Noble ME, Payne SL, Revill CH, Riedinger C, Xu Q, Lunec J: Isoindolinone inhibitors of the murine double minute 2 (MDM2)-p53 protein-protein interaction: structure-activity studies leading to improved potency. J Med Chem 2011, 54:1233-1243.
[370]Burdack C, Kalinsky C, Ross G, Weber L, Khazak V: Pyrrolidin-2-ones as hdm2 ligands. Priaxon Ag 2010, WO 2010028862.
[371]Essmann F, Schulze-Osthoff K: Translational approaches targeting the p53 pathway for anti-cancer therapy. Br J Pharmacol 2012, 165:328-344.
[372]Bogen SL, Ma Y, Wang Y, Lahue BR, Nair LG, Shizuka M, Voss ME, Kirova-Snover M, Pan W, Tian Y, Kulkarni BA, Gibeau CR, Liu Y, Scapin G, Rindgen D, Doll RJ, Guzi TJ, Hicklin DJ, Nomeir A, Seide Dugan C, Shipps GW Jr, Maccoss M: Substituted piperidines that increase p53 activity and the uses thereof. 2011, WO 2011046771A1.
[373]Bertamino A, Soprano M, Musella S, Rusciano MR, Sala M, Vernieri E, Di Sarno V, Limatola A, Carotenuto A, Cosconati S, Grieco P, Novellino E, Illario M, Campiglia P, Gomez-Monterrey I: Synthesis, in vitro: and in cell studies of a new series of [indoline3,2thiazolidine]-based p53 modulators. J Med Chem 2013, 56:5407-5421.
[374]Galatin PS, Abraham DJ: A nonpeptidic sulfonamide inhibits the p53mdm2 interaction and activates p53dependent transcription in mdm2overexpressing cells. J Med Chem 2004, 47:4163-4165.
[375]Ding Q, Zhang Z, Liu JJ, Jiang N, Zhang J, Ross TM, Chu XJ, Bartkovitz D, Podlaski F, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B: Discovery of RG7388, a Potent and Selective p53-MDM2 Inhibitor in Clinical Development. J Med Chem 2013, 56:5979-5983.
[376]Zhang Z, Chu XJ, Liu JJ, Ding Q, Zhang J, Bartkovitz D, Jiang N, Karnachi P, So SS, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev L, Graves B: Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development. ACS Med Chem Lett 2013, 5:124-127.
[377]Lucas BS, Fisher B, McGee LR, Olson SH, Medina JC, Cheung E: An expeditious synthesis of the MDM2-p53 inhibitor AM-8553. J Am Chem Soc 2012, 134:12855-12860.
[378]Sun D, Li Z, Rew Y, Gribble M, Bartberger MD, Beck HP, Canon J, Chen A, Chen X, Chow D, Deignan J, Duquette J, Eksterowicz J, Fisher B, Fox BM, Fu J, Gonzalez AZ, Gonzalez-Lopez De Turiso F, Houze JB, Huang X, Jiang M, Jin L, Kayser F, Liu JJ, Lo MC, Long AM, Lucas B, McGee LR, McIntosh J, Mihalic J, et al.: Discovery of AMG 232, a potent, selective, and orally bioavailable MDM2-p53 inhibitor in clinical development. J Med Chem 2014, 57:1454-1472.
[379]Leão M, Pereira C, Bisio A, Ciribilli Y, Paiva AM, Machado N, Palmeira A, Fernandes MX, Sousa E, Pinto M, Inga A, Saraiva L: Discovery of a new small-molecule inhibitor of p53-MDM2 interaction using a yeast-based approach. Biochem Pharmacol 2013, 85:1234-1245.
[380]Zheng GH, Shen JJ, Zhan YC, Yi H, Xue ST, Wang Z, Ji XY, Li ZR: Design, synthesis and in vitro and in vivo antitumour activity of 3-benzylideneindolin-2-one derivatives, a novel class of small-molecule inhibitors of the MDM2-p53 interaction. Eur J Med Chem 2014, 81C:277-288.
[381]Bykov VJ, Issaeva N, Shilov A, Hultcrantz M, Pugacheva E, Chumakov P, Bergman J, Wiman KG, Selivanova G: Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med 2002, 8:282-288.
[382]Zache N, Lambert JM, Wiman KG, Bykov VJ: PRIMA-1MET inhibits growth of mouse tumors carrying mutant p53. Cell Oncol 2008, 30:411-418.
[383]Zandi R, Selivanova G, Christensen CL, Gerds TA, Willumsen BM, Poulsen HS: PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53. Clin Cancer Res 2011, 17:2830-2841.
[384]Lambert JM, Gorzov P, Veprintsev DB, Soderqvist M, Segerback D, Bergman J, Fersht AR, Hainaut P, Wiman KG, Bykov VJ: PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer Cell 2009, 15:376-388.
[385]Shalom-Feuerstein R, Serror L, Aberdam E, Muller FJ, van Bokhoven H, Wiman KG, Zhou H, Aberdam D, Petit I: Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET. Proc Natl Acad Sci U S A 2013, 110:2152-2156.
[386]Shen J, van den Bogaard EH, Kouwenhoven EN, Bykov VJ, Rinne T, Zhang Q, Tjabringa GS, Gilissen C, van Heeringen SJ, Schalkwijk J, van Bokhoven H, Wiman KG, Zhou H: APR-246/PRIMA-1(MET) rescues epidermal differentiation in skin keratinocytes derived from EEC syndrome patients with p63 mutations. Proc Natl Acad Sci U S A 2013, 110:2157-2162.
[387]Stegh AH: Targeting the p53 signaling pathway in cancer therapy - the promises, challenges and perils. Expert Opin Ther Targets 2012, 16:67-83.
[388]Linde L, Kerem B: Introducing sense into nonsense in treatments of human genetic diseases. Trends Genet 2008, 24:552-563.
[389]Rowe SM, Clancy JP: Pharmaceuticals targeting nonsense mutations in genetic diseases: progress in development. BioDrugs 2009, 23:165-174.
[390]Floquet C, Deforges J, Rousset JP, Bidou L: Rescue of non-sense mutated p53 tumor suppressor gene by aminoglycosides. Nucleic Acids Res 2011, 39:3350-3362.
[391]Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, Pramanik A, Selivanova G: Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 2004, 10:1321-1328.
[392]MacCallum DE, Melville J, Frame S, Watt K, Anderson S, Gianella-Borradori A, Lane DP, Green SR: Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1. Cancer Res 2005, 65:5399-5407.
[393]Choong ML, Yang H, Lee MA, Lane DP: Specific activation of the p53 pathway by low dose actinomycin D: a new route to p53 based cyclotherapy. Cell Cycle 2009, 8:2810-2818.
[394]Smart P, Lane EB, Lane DP, Midgley C, Vojtesek B, Lain S: Effects on normal fibroblasts and neuroblastoma cells of the activation of the p53 response by the nuclear export inhibitor leptomycin B. Oncogene 1999, 18:7378-7386.
[395]Blank JL, Liu XJ, Cosmopoulos K, Bouck DC, Garcia K, Bernard H, Tayber O, Hather G, Liu R, Narayanan U, Milhollen MA, Lightcap ES: Novel DNA damage checkpoints mediating cell death induced by the NEDD8-activating enzyme inhibitor MLN4924. Cancer Res 2013, 73:225-234.
[396]Lain S, Hollick JJ, Campbell J, Staples OD, Higgins M, Aoubala M, McCarthy A, Appleyard V, Murray KE, Baker L, Thompson A, Mathers J, Holland SJ, Stark MJ, Pass G, Woods J, Lane DP, Westwood NJ: Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell 2008, 13:454-463.
[397]Sabeti PC, Varilly P, Fry B, Lohmueller J, Hostetter E, Cotsapas C, Xie X, Byrne EH, McCarroll SA, Gaudet R, Schaffner SF, Lander ES, Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, Gibbs RA, Belmont JW, Boudreau A, Hardenbol P, Leal SM, Pasternak S, Wheeler DA, Willis TD, Yu F, Yang H, Zeng C, Gao Y, Hu H, et al.: Genome-wide detection and characterization of positive selection in human populations. Nature 2007, 449:913-918.
[398]Nakamura Y, Kato H, Nishikawa T, Iwasaki N, Suwa Y, Rotinsulu H, Losung F, Maarisit W, Mangindaan RE, Morioka H, Yokosawa H, Tsukamoto S: Siladenoserinols A-L: new sulfonated serinol derivatives from a tunicate as inhibitors of p53-Hdm2 interaction. Org Lett 2012, 15:322-325.
[399]Vogelstein B, Kinzler KW: Cancer genes and the pathways they control. Nat Med 2004, 10:789-799.
[400]Gasparian AV, Neznanov N, Jha S, Galkin O, Moran JJ, Gudkov AV, Gurova KV, Komar AA: Inhibition of encephalomyocarditis virus and poliovirus replication by quinacrine: implications for the design and discovery of novel antiviral drugs. J Virol 2010, 84:9390-9397.
[401]Draetta GF, Depinho RA: Cancer drug discovery faces the FACT. Sci Transl Med 2011, 3:95ps34.
[402]Reinberg D, Sims RJ 3rd: de FACTo nucleosome dynamics. J Biol Chem 2006, 281:23297-23301.
[403]Orphanides G, LeRoy G, Chang CH, Luse DS, Reinberg D: FACT, a factor that facilitates transcript elongation through nucleosomes. Cell 1998, 92:105-116.
[404]Bruhn SL, Pil PM, Essigmann JM, Housman DE, Lippard SJ: Isolation and characterization of human cDNA clones encoding a high mobility group box protein that recognizes structural distortions to DNA caused by binding of the anticancer agent cisplatin. Proc Natl Acad Sci U S A 1992, 89:2307-2311.
[405]Whittaker SR, Walton MI, Garrett MD, Workman P: The Cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) inhibits retinoblastoma protein phosphorylation, causes loss of Cyclin D1, and activates the mitogen-activated protein kinase pathway. Cancer Res 2004, 64:262-272.
[406]Marshall NF, Price DH: Control of formation of two distinct classes of RNA polymerase II elongation complexes. Mol Cell Biol 1992, 12:2078-2090.
[407]Demidenko ZN, Blagosklonny MV: Flavopiridol induces p53 via initial inhibition of Mdm2 and p21 and, independently of p53, sensitizes apoptosis-reluctant cells to tumor necrosis factor. Cancer Res 2004, 64:3653-3660.
[408]Wu X, Bayle JH, Olson D, Levine AJ: The p53-mdm-2 autoregulatory feedback loop. Genes Dev 1993, 7:1126-1132.
[409]Parks DJ, LaFrance LV, Calvo RR, Milkiewicz KL, Marugan JJ, Raboisson P, Schubert C, Koblish HK, Zhao S, Franks CF, Lattanze J, Carver TE, Cummings MD, Maguire D, Grasberger BL, Maroney AC, Lu T: Enhanced pharmacokinetic properties of 1,4-benzodiazepine-2,5-dione antagonists of the HDM2-p53 protein-protein interaction through structure-based drug design. Bioorg Med Chem Lett 2006, 16:3310-3314.
[410]Kayali R, Ku JM, Khitrov G, Jung ME, Prikhodko O, Bertoni C: Read-through compound 13 restores dystrophin expression and improves muscle function in the mdx mouse model for Duchenne muscular dystrophy. Hum Mol Genet 2012, 21:4007-4020.

Journal of Inflammation
Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa B and p53 mutual antagonism

Mahadeb Pal³ Subhash C Mandal² Narayan C Mandal¹ Asif Ali³ Ashish Bhattacharjee⁴ Srabani Pal²
[1] Department of Botany, Visva-Bharati, Santiniketan-731236, India;Pharmacognosy and Phytotherapy laboratory, Division of Pharmacognosy, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India;Division of Molecular Medicine, Bose Institute, Kolkata 700054, India;Department of Biotechnology, National Institute of Technology, Durgapur-713209, India
关键词: Inhibitor of kappaB kinase (IKK); Inhibitor of kB (I κB); MDM2; Tumor suppressor p53 (TP53); Lipopolysachharides (LPS); Tumor necrosis factor (TNF); Toll like receptor (TLR); Small molecule inhibitors; Chemoprevention; Phytochemicals; Cancer; Inflammation; Nuclear factor kappa B (NF- κB);
Others : 1140831 DOI : 10.1186/1476-9255-11-23

received in 2014-01-24, accepted in 2014-06-28, 发布年份 2014
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