Nuclear factor-κB inhibitors as sensitizers to anticancer drugs

The cytotoxicity of chemotherapeutic agents is attributed to apoptosis. Acquired resistance to the effects of chemotherapy has emerged as a significant impediment to effective cancer therapy. One feature that cytotoxic treatments of cancer have in common is their activation of the transcription factor nuclear factor-κB (NF-κB), which regulates cell survival. NF-κB activation suppresses the apoptotic potential of chemotherapeutic agents and contributes to resistance. What evidence is there that inhibitors of NF-κB might promote apoptosis in cancer cells and can NF-κB inhibitors be used to overcome resistance to chemotherapeutic agents?

[1]  P. Dent,et al.  Contribution of Disruption of the Nuclear Factor-κB Pathway to Induction of Apoptosis in Human Leukemia Cells by Histone Deacetylase Inhibitors and Flavopiridol , 2004, Molecular Pharmacology.

[2]  P. Tassone,et al.  NF-κB/Rel-mediated regulation of apoptosis in hematologic malignancies and normal hematopoietic progenitors , 2004, Leukemia.

[3]  R. Schmid,et al.  Suppression of NF-κB activity by sulfasalazine is mediated by direct inhibition of IκB kinases α and β , 2000 .

[4]  G. Sledge,et al.  Paclitaxel sensitivity of breast cancer cells with constitutively active NF-κB is enhanced by IκBα super-repressor and parthenolide , 2000, Oncogene.

[5]  S. Venuta,et al.  Rapamycin inhibits doxorubicin-induced NF-kappaB/Rel nuclear activity and enhances the apoptosis of melanoma cells. , 2004, European journal of cancer.

[6]  A. D. Rodrigues,et al.  Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. , 1996, The Journal of pharmacology and experimental therapeutics.

[7]  S. Manna,et al.  Human Chorionic Gonadotropin Decreases Proliferation and Invasion of Breast Cancer MCF-7 Cells by Inhibiting NF-κB and AP-1 Activation* , 2004, Journal of Biological Chemistry.

[8]  S. Grant,et al.  The cyclin-dependent kinase inhibitor flavopiridol disrupts sodium butyrate-induced p21WAF1/CIP1 expression and maturation while reciprocally potentiating apoptosis in human leukemia cells. , 2002, Molecular cancer therapeutics.

[9]  M. Karin,et al.  The two NF-κB activation pathways and their role in innate and adaptive immunity , 2004 .

[10]  J. Inoue,et al.  Inhibition of Tumor Necrosis Factor-α-induced Nuclear Translocation and Activation of NF-κB by Dehydroxymethylepoxyquinomicin* , 2002, The Journal of Biological Chemistry.

[11]  B. Aggarwal,et al.  Guggulsterone Inhibits NF-κB and IκBα Kinase Activation, Suppresses Expression of Anti-apoptotic Gene Products, and Enhances Apoptosis* , 2004, Journal of Biological Chemistry.

[12]  J. Geng,et al.  Andrographolide Attenuates Inflammation by Inhibition of NF-κB Activation through Covalent Modification of Reduced Cysteine 62 of p501 , 2004, The Journal of Immunology.

[13]  L. Boxer,et al.  NF-kappa B sites function as positive regulators of expression of the translocated c-myc allele in Burkitt's lymphoma , 1994, Molecular and cellular biology.

[14]  J. Inoue,et al.  Synthesis of NF-κB activation inhibitors derived from epoxyquinomicin C , 2000 .

[15]  G. Gasparini,et al.  Inhibitors of cyclo-oxygenase 2: a new class of anticancer agents? , 2003, The Lancet. Oncology.

[16]  Frank Pajonk,et al.  The human immunodeficiency virus (HIV)-1 protease inhibitor saquinavir inhibits proteasome function and causes apoptosis and radiosensitization in non-HIV-associated human cancer cells. , 2002, Cancer research.

[17]  G. Wahl,et al.  p53 stabilization is decreased upon NFκB activation , 2002 .

[18]  R. Bold,et al.  Inhibition of AKT abrogates chemotherapy-induced NF-kappaB survival mechanisms: implications for therapy in pancreatic cancer. , 2004, Journal of the American College of Surgeons.

[19]  L. Boscá,et al.  Interleukin‐4 and interleukin‐10 modulate nuclear factor κB activity and nitric oxide synthase‐2 expression in Theiler's virus‐infected brain astrocytes , 2002, Journal of neurochemistry.

[20]  P. Kloetzel,et al.  Green Tea Epigallocatechin-3-Gallate Mediates T Cellular NF-κB Inhibition and Exerts Neuroprotection in Autoimmune Encephalomyelitis1 , 2004, The Journal of Immunology.

[21]  L. Marnett,et al.  Aspirin-like molecules that covalently inactivate cyclooxygenase-2. , 1998, Science.

[22]  J. Schulte‐Mönting,et al.  Quantitative structure-activity relationship of sesquiterpene lactones as inhibitors of the transcription factor NF-kappaB. , 2004, Journal of medicinal chemistry.

[23]  C. Der,et al.  Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K , 1997, Nature.

[24]  G. Schwartz,et al.  Sequential dependent enhancement of caspase activation and apoptosis by flavopiridol on paclitaxel-treated human gastric and breast cancer cells. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[25]  J. Karp,et al.  Timed sequential therapy of acute leukemia with flavopiridol: in vitro model for a phase I clinical trial. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[26]  M. Falchi,et al.  HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma , 2002, Nature Medicine.

[27]  S. Wright,et al.  Inhibitory effect of growth hormone on TNF-alpha secretion and nuclear factor-kappaB translocation in lipopolysaccharide-stimulated human monocytes. , 1997, Journal of immunology.

[28]  A. Arlt,et al.  Role of NF-κB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death , 2003, Oncogene.

[29]  R. Weichselbaum,et al.  Ionizing radiation induces expression and binding activity of the nuclear factor kappa B. , 1991, The Journal of clinical investigation.

[30]  S. Grant,et al.  The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in human leukemia cells (U937) through the mitochondrial rather than the receptor-mediated pathway , 2001, Cell Death and Differentiation.

[31]  David R. Jones,et al.  Proteasome inhibition sensitizes non-small-cell lung cancer to gemcitabine-induced apoptosis. , 2004, The Annals of thoracic surgery.

[32]  G. Wilding,et al.  Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase inhibitor flavopiridol , 2002, Cancer Chemotherapy and Pharmacology.

[33]  R. Gaynor,et al.  Enhanced Chemosensitivity to Irinotecan by RNA Interference-Mediated Down-Regulation of the Nuclear Factor-κB p65 Subunit , 2004, Clinical Cancer Research.

[34]  M. Watabe,et al.  Caffeic Acid Phenethyl Ester Induces Apoptosis by Inhibition of NFκB and Activation of Fas in Human Breast Cancer MCF-7 Cells* , 2004, Journal of Biological Chemistry.

[35]  R. Jain,et al.  The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis , 2004, Nature.

[36]  A I Pick,et al.  THE TREATMENT OF MULTIPLE MYELOMA , 1948, Harefuah.

[37]  K. Schulze-Osthoff,et al.  The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB , 1996, The Journal of experimental medicine.

[38]  Sankar Ghosh,et al.  Signaling to NF-kappaB. , 2004, Genes & development.

[39]  E. Kikuchi,et al.  Suppression of hormone-refractory prostate cancer by a novel nuclear factor kappaB inhibitor in nude mice. , 2003, Cancer research.

[40]  M. Tomonaga,et al.  Constitutive Activation Of Nf- κ B In Primary Adult T-cell Leukemia Cells , 1999 .

[41]  B. Aggarwal,et al.  Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[42]  N. Magné,et al.  Activation of Nuclear Factor κB through the IKK Complex by the Topoisomerase Poisons SN38 and Doxorubicin: A Brake to Apoptosis in HeLa Human Carcinoma Cells , 2001 .

[43]  R. Gaynor,et al.  Sulindac Inhibits Activation of the NF-κB Pathway* , 1999, The Journal of Biological Chemistry.

[44]  B. Aggarwal,et al.  Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates TNF-induced NF-kappa B activation through inhibition of activation of I kappa B alpha kinase and Akt in human non-small cell lung carcinoma: correlation with suppression of COX-2 synthesis. , 2004, Journal of immunology.

[45]  R. Bold,et al.  Chemosensitization of pancreatic cancer by inhibition of the 26S proteasome. , 2001, The Journal of surgical research.

[46]  Marty W. Mayo,et al.  TNF- and Cancer Therapy-Induced Apoptosis: Potentiation by Inhibition of NF-κB , 1996, Science.

[47]  M. Karin,et al.  Cytoskeletal control of gene expression: depolymerization of microtubules activates NF-kappa B , 1995, The Journal of cell biology.

[48]  R. Gaynor,et al.  The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β , 1998, Nature.

[49]  Robert J. Moore,et al.  An Anti-Tumor Necrosis Factor-α Antibody Inhibits the Development of Experimental Skin Tumors , 2003 .

[50]  J. Cusack,et al.  Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB , 1999, Nature Medicine.

[51]  Masafumi Ohtsubo,et al.  Constitutive activation of nuclear factor-κB prevents TRAIL-induced apoptosis in renal cancer cells , 2001, Oncogene.

[52]  S. Lowe,et al.  Intrinsic tumour suppression , 2004, Nature.

[53]  N. Munshi,et al.  NF-κB as a Therapeutic Target in Multiple Myeloma* , 2002, The Journal of Biological Chemistry.

[54]  C. Sigmund,et al.  Ghrelin Inhibits Proinflammatory Responses and Nuclear Factor-κB Activation in Human Endothelial Cells , 2004, Circulation.

[55]  Joseph A. DiDonato,et al.  Immunosuppression by Glucocorticoids: Inhibition of NF-κB Activity Through Induction of IκB Synthesis , 1995, Science.

[56]  René Bernards,et al.  Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-κB , 2003, Nature.

[57]  J C Reed,et al.  IAP family proteins--suppressors of apoptosis. , 1999, Genes & development.

[58]  W. Hong,et al.  Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplification , 1998, Oncogene.

[59]  M. Madsen,et al.  Anticancer agent CHS 828 suppresses nuclear factor‐κB activity in cancer cells through downregulation of IKK activity , 2004, International Journal of Cancer.

[60]  Hiroki Sato,et al.  Matrix Metalloproteinase 9 Expression Is Induced by Epstein-Barr Virus Latent Membrane Protein 1 C-Terminal Activation Regions 1 and 2 , 1999, Journal of Virology.

[61]  S. Manna,et al.  IL-13 suppresses TNF-induced activation of nuclear factor-kappa B, activation protein-1, and apoptosis. , 1998, Journal of immunology.

[62]  Michael Karin,et al.  Activation by IKKα of a Second, Evolutionary Conserved, NF-κB Signaling Pathway , 2001, Science.

[63]  M. Read,et al.  Enhanced Chemosensitivity to Irinotecan by RNA Interference-Mediated Down-Regulation of the NF-B p 65 Subunit , 2004 .

[64]  M. Tomonaga,et al.  Bay 11-7082 inhibits transcription factor NF-kappaB and induces apoptosis of HTLV-I-infected T-cell lines and primary adult T-cell leukemia cells. , 2002, Blood.

[65]  L. Pfeffer,et al.  NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase , 1999, Nature.

[66]  Beverly S Mitchell,et al.  Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[67]  Yiwei Li,et al.  Inactivation of NF-κB by genistein is mediated via Akt signaling pathway in breast cancer cells , 2003, Oncogene.

[68]  G. Kundu,et al.  Nuclear Factor-inducing Kinase Plays a Crucial Role in Osteopontin-induced MAPK/IκBα Kinase-dependent Nuclear Factor κB-mediated Promatrix Metalloproteinase-9 Activation* , 2004, Journal of Biological Chemistry.

[69]  B. Aggarwal,et al.  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. , 2004, The Journal of biological chemistry.

[70]  V. Adhami,et al.  Lupeol modulates NF-κB and PI3K/Akt pathways and inhibits skin cancer in CD-1 mice , 2004, Oncogene.

[71]  N. Perkins,et al.  Transcriptional Cross Talk between NF-κB and p53 , 1999, Molecular and Cellular Biology.

[72]  A. Baldwin,et al.  Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. , 2000, Cancer research.

[73]  Rolf Larsson,et al.  A Phase I study of CHS 828 in patients with solid tumor malignancy. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[74]  M. Gerritsen,et al.  Novel Inhibitors of Cytokine-induced IκBα Phosphorylation and Endothelial Cell Adhesion Molecule Expression Show Anti-inflammatory Effects in Vivo* , 1997, The Journal of Biological Chemistry.

[75]  N. Perkins,et al.  Active Repression of Antiapoptotic Gene Expression by RelA(p65) NF-κB , 2004 .

[76]  C. Thiemermann,et al.  Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[77]  P. Elliott,et al.  Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. , 2001, Cancer research.

[78]  R. Larsson,et al.  The combination of the antitumoural pyridyl cyanoguanidine CHS 828 and etoposide in vitro–from cytotoxic synergy to complete inhibition of apoptosis , 2002, British journal of pharmacology.

[79]  I. Verma,et al.  IκB Kinase-Independent IκBα Degradation Pathway: Functional NF-κB Activity and Implications for Cancer Therapy , 2003, Molecular and Cellular Biology.

[80]  Kazuhiro Takahashi,et al.  Inhibition of NFκB Increases the Efficacy of Cisplatin in in Vitro and in Vivo Ovarian Cancer Models* , 2004, Journal of Biological Chemistry.

[81]  H. Kalthoff,et al.  Inhibition of NF-κB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin , 2001, Oncogene.

[82]  B. Rayet,et al.  Aberrant rel/nfkb genes and activity in human cancer , 1999, Oncogene.

[83]  M. Yao,et al.  A Selective IKK-2 Inhibitor Blocks NF-κB-dependent Gene Expression in Interleukin-1β-stimulated Synovial Fibroblasts* , 2003, Journal of Biological Chemistry.

[84]  S. Gerstberger,et al.  Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation , 1995, Science.

[85]  Robert S. Kerbel,et al.  The anti-angiogenic basis of metronomic chemotherapy , 2004, Nature Reviews Cancer.

[86]  B. Aggarwal,et al.  Nuclear factor‐κB and IκB kinase are constitutively active in human pancreatic cells, and their down‐regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis , 2004, Cancer.

[87]  C. White,et al.  Activation of NF-kappaB by antineoplastic agents. Role of protein kinase C. , 1997, The Journal of biological chemistry.

[88]  P. Szlosarek,et al.  Tumour necrosis factor α: a potential target for the therapy of solid tumours , 2003 .

[89]  P. Szlosarek,et al.  Tumour necrosis factor alpha: a potential target for the therapy of solid tumours. , 2003, The Lancet. Oncology.

[90]  R. Perona,et al.  Cell stress and MEKK1-mediated c-Jun activation modulate NFkappaB activity and cell viability. , 2002, Molecular biology of the cell.

[91]  Y. Ben-Neriah,et al.  NF-κB functions as a tumour promoter in inflammation-associated cancer , 2004, Nature.

[92]  Sujay K. Singh,et al.  Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor‐κB signaling , 2004 .

[93]  P. Elliott,et al.  26S proteasome inhibition induces apoptosis and limits growth of human pancreatic cancer , 2001, Journal of cellular biochemistry.

[94]  J. Cusack,et al.  Inducible chemoresistance to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothe cin (CPT-11) in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kappaB activation. , 2000, Cancer research.

[95]  David R. Jones,et al.  Combined histone deacetylase and NF-kappaB inhibition sensitizes non-small cell lung cancer to cell death. , 2004, Surgery.

[96]  C. Bucana,et al.  Nuclear Factor-κB Activity Correlates with Growth, Angiogenesis, and Metastasis of Human Melanoma Cells in Nude Mice , 2000 .

[97]  Francesca Zazzeroni,et al.  Induction of gadd45β by NF-κB downregulates pro-apoptotic JNK signalling , 2001, Nature.

[98]  D. Conrad,et al.  Interruption of the NF-kappaB pathway by Bay 11-7082 promotes UCN-01-mediated mitochondrial dysfunction and apoptosis in human multiple myeloma cells. , 2004, Blood.

[99]  Marianne Fillet,et al.  NF-κB transcription factor induces drug resistance through MDR1 expression in cancer cells , 2003, Oncogene.

[100]  D. Schrump,et al.  Potentiation of paclitaxel cytotoxicity in lung and esophageal cancer cells by pharmacologic inhibition of the phosphoinositide 3-kinase/protein kinase B (Akt)-mediated signaling pathway. , 2004, The Journal of thoracic and cardiovascular surgery.

[101]  Michael Karin,et al.  IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer , 2004, Cell.

[102]  O. Sterner,et al.  Cycloepoxydon, 1-hydroxy-2-hydroxymethyl-3-pent-1-enylbenzene and 1-hydroxy-2-hydroxymethyl-3-pent-1,3-dienylbenzene, new inhibitors of eukaryotic signal transduction. , 1998, The Journal of antibiotics.

[103]  A. Burny,et al.  Potentiation of Tumor Necrosis Factor-Induced NF-κB Activation by Deacetylase Inhibitors Is Associated with a Delayed Cytoplasmic Reappearance of IκBα , 2003, Molecular and Cellular Biology.

[104]  R. Sartor,et al.  The IκB/NF-κB system: a key determinant of mucosal inflammation and protection , 2000 .

[105]  M. Reitz,et al.  Antitumorigenic effects of HIV protease inhibitor ritonavir: inhibition of Kaposi sarcoma. , 2002, Blood.

[106]  A. Lentsch,et al.  In vivo suppression of NF-kappa B and preservation of I kappa B alpha by interleukin-10 and interleukin-13. , 1997, The Journal of clinical investigation.

[107]  Y. Ohtsuki,et al.  HIV-1 Protease Inhibitor, Ritonavir , 2004, Cancer Research.

[108]  D. Howard,et al.  Preferential induction of apoptosis for primary human leukemic stem cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[109]  G. Cheng,et al.  Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-κB inhibition , 2000, Oncogene.

[110]  K. Shakesheff,et al.  Alpha-MSH inhibits inflammatory signalling in Schwann cells. , 2004, Neuroreport.

[111]  M. Karin,et al.  Inhibition of JNK activation through NF-κB target genes , 2001, Nature.

[112]  Yang Shi,et al.  Ineffectiveness of Histone Deacetylase Inhibitors to Induce Apoptosis Involves the Transcriptional Activation of NF-κB through the Akt Pathway* , 2003, Journal of Biological Chemistry.

[113]  Z. Estrov,et al.  Resveratrol blocks interleukin-1beta-induced activation of the nuclear transcription factor NF-kappaB, inhibits proliferation, causes S-phase arrest, and induces apoptosis of acute myeloid leukemia cells. , 2003, Blood.

[114]  E. Sausville,et al.  Proteasome inhibitors: a novel class of potent and effective antitumor agents. , 1999, Cancer research.

[115]  B. Aggarwal,et al.  Cyclooxygenase (COX)-2 Inhibitor Celecoxib Abrogates TNF-Induced NF-κB Activation through Inhibition of Activation of IκBα Kinase and Akt in Human Non-Small Cell Lung Carcinoma: Correlation with Suppression of COX-2 Synthesis1 , 2004, The Journal of Immunology.

[116]  C. White,et al.  Activation of NF-κB by Antineoplastic Agents , 1997, The Journal of Biological Chemistry.

[117]  Shadan Ali,et al.  Apoptosis-Inducing Effect of Chemotherapeutic Agents Is Potentiated by Soy Isoflavone Genistein, a Natural Inhibitor of NF-κB in BxPC-3 Pancreatic Cancer Cell Line , 2004, Pancreas.

[118]  S. Srivastava,et al.  Cell cycle arrest, apoptosis induction and inhibition of nuclear factor kappa B activation in anti-proliferative activity of benzyl isothiocyanate against human pancreatic cancer cells. , 2004, Carcinogenesis.

[119]  B. Aggarwal,et al.  Induction of Cell Cycle Arrest and Apoptosis by the Proteasome Inhibitor PS-341 in Hodgkin Disease Cell Lines Is Independent of Inhibitor of Nuclear Factor-κB Mutations or Activation of the CD30, CD40, and RANK Receptors , 2004, Clinical Cancer Research.

[120]  J. Adams,et al.  Novel IKK inhibitors: β-carbolines , 2003 .

[121]  B. Aggarwal,et al.  Flavopiridol Inhibits NF-κB Activation Induced by Various Carcinogens and Inflammatory Agents through Inhibition of IκBα Kinase and p65 Phosphorylation , 2004, Journal of Biological Chemistry.

[122]  D. Braguer,et al.  Involvement of nuclear factor kappaB in c-Myc induction by tubulin polymerization inhibitors. , 2001, Molecular pharmacology.

[123]  Gi-Young Kim,et al.  Lycopene suppresses the lipopolysaccharide‐induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen‐activated protein kinases and nuclear factor‐κB , 2004, Immunology.

[124]  James R. Burke,et al.  BMS-345541 Is a Highly Selective Inhibitor of IκB Kinase That Binds at an Allosteric Site of the Enzyme and Blocks NF-κB-dependent Transcription in Mice* , 2003, The Journal of Biological Chemistry.

[125]  D. Braguer,et al.  Opposite effects of antimicrotubule agents on c-myc oncogene expression depending on the cell lines used. , 2000, European journal of cancer.

[126]  J. Piette,et al.  Topoisomerase poisons activate the transcription factor NF-kappaB in ACH-2 and CEM cells. , 1996, Nucleic acids research.

[127]  Bart Barlogie,et al.  A phase 2 study of bortezomib in relapsed, refractory myeloma. , 2003, The New England journal of medicine.

[128]  T. Anke,et al.  Inhibition of NF-kappa B activation by panepoxydone. , 1996, Biochemical and biophysical research communications.

[129]  R. Daynes,et al.  Nuclear factor kappaB inhibitors induce adhesion-dependent colon cancer apoptosis: implications for metastasis. , 2002, Cancer research.

[130]  A. Shevchenko,et al.  Activation of Transcription Factor NF-κB Requires ELKS, an IκB Kinase Regulatory Subunit , 2004, Science.

[131]  M. Mayo,et al.  Combined proteasome and histone deacetylase inhibition in non-small cell lung cancer. , 2004, The Journal of thoracic and cardiovascular surgery.

[132]  Cytoskeletal Control of Gene Expression : Depolymerization of Microtubules Activates NF-xB , 2002 .

[133]  Kevin M. Ryan,et al.  Mechanistic and Predictive Profiling of 5-Fluorouracil Resistance in Human Cancer Cells , 2004, Cancer Research.

[134]  J. Adams The proteasome: a suitable antineoplastic target , 2004, Nature Reviews Cancer.

[135]  S. Jee,et al.  Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. , 2001, Anticancer research.

[136]  G. Vassal,et al.  Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-κB activity , 2003, British Journal of Cancer.

[137]  R. Schmid,et al.  Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. , 1998, The Journal of clinical investigation.

[138]  M. Karin,et al.  Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. , 2000, Annual review of immunology.

[139]  R. Chetty,et al.  Cyclin D1 and human neoplasia. , 1998, Molecular pathology : MP.

[140]  M. Tomonaga,et al.  Constitutive Activation of NF-κB in Primary Adult T-Cell Leukemia Cells , 1999 .

[141]  Michael Karin,et al.  NF-κB in cancer: from innocent bystander to major culprit , 2002, Nature Reviews Cancer.

[142]  M. Goldman,et al.  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 , 2002 .

[143]  D. Conrad,et al.  Interruption of the NF-B pathway by Bay 11-7082 promotes UCN-01 – mediated mitochondrial dysfunction and apoptosis in human multiple myeloma cells , 2003 .