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Hu et al., J Biol Chem 1999 (Breast Neoplasms) : These findings suggest that TRAIL receptors induce apoptosis, NF-kappaB and JNK activation through distinct signaling pathways, and activation of NF-kappaB is not sufficient for protecting cells from TRAIL induced apoptosis
Mühlenbeck et al., J Biol Chem 2000 : Overexpression of the tumor necrosis factor (TNF) related apoptosis inducing ligand ( TRAIL ) receptors, TRAIL-R1 and TRAIL-R2, induces apoptosis and activation of NF-kappaB in cultured cells ... Moreover, in these cell lines interleukin-6 secretion and NF-kappaB activation were induced by cross linked or non-cross linked anti-TRAIL , as well as by both receptor-specific IgGs
Yamanaka et al., Hepatology 2000 (Carcinoma, Hepatocellular...) : Despite the expression of TRAIL-R1 and -R2, all 6 HCC cell lines showed resistance to TRAIL induced apoptosis with no relation to nuclear factor kappa B (NF-kappaB) levels induced by TRAIL ... Actinomycin D and camptothecin almost completely suppressed NF-kappaB induction by TRAIL , whereas doxorubicin had little effect
Pawlowski et al., Anticancer Res 2000 (Carcinoma, Renal Cell...) : NF-kappa B , although stimulated in these cell lines, does not play a role in the sensitivity of RCC to TRAIL and could play other functions in TRAIL signaling
Franco et al., J Immunol 2001 (Melanoma) : The role of NF-kappa B in TNF related apoptosis inducing ligand ( TRAIL ) -induced apoptosis of melanoma cells ... It is also known that TNF related apoptosis inducing ligand ( TRAIL ) can activate NF-kappaB through the death receptors TRAIL-R1 and TRAIL-R2, and decoy receptor TRAIL-R4 ... Furthermore, studies with NF-kappaB reporter constructs revealed that the resistance of melanoma lines to TRAIL induced apoptosis was correlated to activation of NF-kappaB in response to TRAIL ... Therefore, these results suggest that activation of NF-kappaB by TRAIL plays an important role in resistance of melanoma cells to TRAIL induced apoptosis and further suggest that inhibitors of NF-kappaB may be useful adjuncts in clinical use of TRAIL against melanoma
Trauzold et al., Oncogene 2001 (Adenocarcinoma...) : We report here that the stimulation of the CD95- and TRAIL-resistant human pancreatic adenocarcinoma cell line PancTuI with an agonistic anti-CD95 antibody or TRAIL resulted in activation of protein kinase C and NF-kappaB ... Inhibition of protein kinase C by Gö6983 sensitized these cells to apoptotic challenges and strongly diminished activation of NF-kappaB by anti-CD95 and TRAIL
Baetu et al., J Immunol 2001 : Disruption of NF-kappaB signaling reveals a novel role for NF-kappaB in the regulation of TNF related apoptosis inducing ligand expression ... In this T cell model, as well as in primary T lymphocytes, expression of TNF related apoptosis inducing ligand ( TRAIL ) apoptotic signaling protein was dramatically down-regulated by inhibition of NF-kappaB binding activity ... Induction of the transdominant repressor of IkappaBalpha dramatically down-regulated surface expression of TRAIL, indicating an essential role for NF-kappaB in the regulation of TRAIL ... The regulation of TRAIL expression by NF-kappaB may represent a general mechanism that contributes to the control of TRAIL mediated apoptosis in T lymphocytes
Mitsiades et al., Expert Opin Investig Drugs 2001 (Multiple Myeloma...) : Moreover, NF-kappaB inhibitors such as SN50 ( a cell permeable inhibitor of NF-kappaB nuclear translocation ) as well as the proteasome inhibitor PS-341, which is currently in Phase II clinical trials, also enhanced the pro-apoptotic activity of TRAIL/Apo2L in MM cells
Kim et al., J Cell Biochem 2002 : DeltaIkappaBalpha suppressed the transactivation of NF-kappaB induced by TNF-alpha or TRAIL , as reflected by luciferase-reporter activity ... Conversely, expression of the p65 subunit of NF-kappaB suppressed TNF-alpha-, TRAIL- , and serum deprivation induced cell death
Mitsiades et al., Oncogene 2002 (Multiple Myeloma) : We have previously shown that Apo2 ligand/TNF Related apoptosis inducing ligand ( Apo2L/TRAIL ) induces apoptosis of MM cells, including cells either sensitive or resistant to Dex and cytotoxic drugs, and overcomes the growth and survival effect of IL-6 ; conversely, NF-kappaB transcriptional activity attenuates their Apo2L/TRAIL-sensitivity
Shetty et al., Apoptosis 2002 : By blocking TRAIL induced NFkappaB activation, the sensitivity of cells to undergo TRAIL induced apoptosis was significantly decreased
Inoue et al., Lab Invest 2002 (Adenocarcinoma...) : Therefore, we investigated TRAIL sensitivity, TRAIL induced nuclear factor-kappaB (NF-kappaB) activation, and expression of TRAIL in human colonic adenocarcinoma cell lines ( HT-29, LS180, SK-CO-1 ) ... Activation of NF-kappaB was variably influenced by TRAIL administration, with no consistent tendency among the cell lines, indicating that TRAIL induced NF-kappaB activation might be cell-type dependent
Kim et al., Hepatology 2002 (Carcinoma, Hepatocellular...) : TRAIL induced NF-kappaB activation was preceded by IkappaBalpha kinase (IKK) activation and IkappaBalpha degradation and depended on TRAF2, NF-kappaB inducing kinase (NIK), IKK1, and IKK2
Qian et al., Zhongguo Shi Yan Xue Ye Xue Za Zhi 2002 (Hematologic Neoplasms) : However, TRAIL can also trigger transcriptional activations of the pro-oncogene of c-fos, JNK, and NF-kappaB by other signaling pathways downstream of FADD/caspase-8
Renshaw et al., J Immunol 2003 : No additional proapoptotic effect of leucine zipper TRAIL was identified following TRAIL treatment of neutrophils in the presence of gliotoxin, an inhibitor of NF-kappaB, suggesting TRAIL does not activate NF-kappaB in human neutrophils
Shigeno et al., Oncogene 2003 (Carcinoma, Hepatocellular...) : On the other hand, TRAIL activated NF-kappa B composed of RelA-p50 heterodimer, a key transcription factor regulating cell survival, in HuH-7 and HepG2 cells ... However, IFN-alpha pretreatment repressed the TRAIL mediated activation of NF-kappaB and decreased its transcriptional activity in HuH-7 but not in HepG2 cells
Secchiero et al., Circulation 2003 (MAP Kinase Signaling System) : Conversely, TRAIL did not activate NF-kappaB or affect the surface expression of the inflammatory markers E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1
Milani et al., J Neurochem 2003 (Neuroblastoma) : TRAIL induced distinct short-term ( 1-60 min ) and long-term ( 3-24 h ) effects on the protein kinase B (PKB)/Akt ( Akt ), extracellular signal regulated kinase ( ERK ), cAMP response element binding protein ( CREB ), nuclear factor kappa B (NF-kappaB) and caspase pathways
Ehrhardt et al., Oncogene 2003 (Acute Disease...) : Our data describe the biological significance of TRAIL mediated activation of NF-kappaB in cancer cells resistant to TRAIL mediated apoptosis : TRAIL leads to an increase in tumor cell count by a prosurvival and possibly mitogenic function
Okano et al., Lab Invest 2003 (Carcinoma, Hepatocellular...) : Furthermore, cFLIP over-expression activated nuclear factor (NF)-kappaB and cFLIP down-regulation attenuated NF-kappaB activation induced by TNF-alpha or TRAIL
Li et al., J Immunol 2003 : In surviving cells, TRAIL activates NF-kappaB , induces expression of E-selectin, ICAM-1, and IL-8, and promotes adhesion of leukocytes
Secchiero et al., J Leukoc Biol 2003 (Acute Disease...) : Moreover, NF-kappaB nuclear translocation induced by TRAIL but not by TNF-alpha was abrogated by z-IETD-fmk, a caspase-8-specific inhibitor
Harper et al., J Biol Chem 2003 : Taken together, these results show that PKC activation specifically inhibits the recruitment of key obligatory death domain containing adaptor proteins to their respective membrane associated signaling complexes, thereby modulating TRAIL induced apoptosis and TNF induced NF-kappaB activation , respectively
Robbins et al., Endocrinology 2003 : In addition, caspase-12 was cleaved, and phosphorylation of eukaryotic initiation factor 2alpha occurred, suggesting that an endoplasmic reticulum stress pathway was involved in addition to NF-kappaB induction of an extrinsic pathway, possibly mediated by TNF related apoptosis inducing ligand
Hao et al., Apoptosis 2003 (Leukemia) : However, CEM cells showed a faster response to TRAIL induced NF-kappaB activation than K562 cells
Wajant et al., Vitam Horm 2004 : Second, TRAIL and some of its receptors are inducible by NFkappaB , disclosing the possibility of autoamplifying TRAIL signaling loops
Kim et al., Cell Mol Life Sci 2004 (Astrocytoma...) : Proteasome inhibitors suppressed TRAIL mediated activation of NF-kappaB ; however, inhibition of the NF-kappaB pathway alone was not sufficient to enhance TRAIL mediated cell death
Rathore et al., J Biol Chem 2004 : The late phase of the TRAIL induced NF-kappaB is critically dependent on caspase 8 and can be blocked by pharmacological and genetic inhibitors of caspase 8 activation, such as benzyloxycarbonyl-VAD-fluoromethyl ketone, benzyloxycarbonyl-IETD-fluoromethyl ketone, and small interfering RNA targeting caspase 8 and FADD ... Whereas caspase 3 is required for TRAIL induced apoptosis, it is not involved in TRAIL induced NF-kappaB activation ... The late phase of TRAIL induced NF-kappaB activation involves caspase mediated cleavage of IkappaBalpha between Asp ( 31 ) and Ser ( 32 ) residues to generate an N-terminal truncated fragment that is degraded by the proteasome via the N-end rule pathway
Wachter et al., J Biol Chem 2004 (Inflammation) : Surprisingly, cFLIP ( L ) specifically blocked TRAIL induced NF-kappaB activation and TRAIL dependent induction of the proinflammatory target gene interleukin-8 ... Taken together, our data demonstrate that cFLIP ( L ) is not only a central antiapoptotic modulator of TRAIL mediated apoptosis but also an inhibitor of TRAIL induced NF-kappaB activation and subsequent proinflammatory target gene expression
Guseva et al., Mol Cancer Res 2004 (Prostatic Neoplasms) : TRAIL effects on mitochondrial NF-kappaB-DNA binding and mitochondrial genome encoded mRNA levels also depend on Bcl-2 overexpression
Matsuda et al., J Virol 2005 (Leukemia-Lymphoma, Adult T-Cell) : Our results suggest that the constitutive activation of NF-kappaB is essential for Apo2L gene induction and protection against Apo2L induced apoptosis and that suppression of NF-kappaB may be a useful adjunct in clinical use of Apo2L against ATL
Davies et al., Cell Signal 2005 (Carcinoma) : The activation of NF-kappaB and phosphatidylinositol-3 (PI3) kinase by TNF-alpha and TRAIL overrides the pro-apoptotic effects of these ligands in carcinoma cells and hinders their therapeutic application
Singh et al., Oncogene 2005 (Breast Neoplasms) : HDAC inhibitors synergized with TRAIL by inducing DRs DR4/TRAIL-R1 and DR5/TRAIL-R2 through NFkappaB activation and some of the proapoptotic members of the Bcl-2 family, and engaging the mitochondrial pathway
Kim et al., Cancer Res 2005 (Carcinoma, Hepatocellular...) : Specifically, it is not yet understood how TRAIL controls nuclear factor kappaB (NF-kappaB) activation and overcomes its anti-apoptotic effect ... We explored the regulation of NF-kappaB activity by TRAIL and its role in apoptosis ... Although TRAIL alone did not induce NF-kappaB activity, TRAIL combined with z-VAD significantly increased NF-kappaB activation ... These results suggest that TRAIL induces NF-kappaB activation, but simultaneously abrogates NF-kappaB activation by cleaving p65, and thereby inhibits the induction of anti-apoptotic proteins such as XIAP, which contributes to the strong apoptotic activity of TRAIL compared with other TNF family members
Siegmund et al., Mol Cell Biol 2005 : Overexpression of FLIP ( L ) and FLIP ( S ) inhibited Fas- as well as TRAIL mediated NF-kappaB activation and apoptosis induction in IFN-gamma primed cells suggesting that both responses are coregulated at the level of the DISC
Hasel et al., Lab Invest 2005 (Fibrosis...) : RelA transcriptional activity increased upon stimulation with IFNgamma and IFNgamma/TRAIL
Chu et al., Cancer Biol Ther 2006 (Carcinoma, Hepatocellular...) : In conclusion : CYLD inhibits TRAIL mediated NF-kappaB activation and enhances the sensitivity of HCC cells to TRAIL triggered apoptosis
Williams et al., Cell Death Differ 2007 (Adenoma...) : Both addition of IGFBP-3 protein to cell cultures or enforced expression of IGFBP-3 in the HT29 carcinoma cell line inhibited nuclear factor kappa B (NF-kappaB) activation in response to the induction of apoptosis by TRAIL
Parsons et al., Oncogene 2006 (Cell Transformation, Neoplastic) : We further show that whereas TMS1/ASC is not required for TNFalpha or TRAIL induced activation of NF-kappaB or caspase-8, it can promote caspase-8 activation independently of death receptor-ligand interactions
Begue et al., Gastroenterology 2006 (Disease Models, Animal...) : TRAIL induced activation of NF-kappaB was determined by electrophoretic mobility shift assay
Malhi et al., Oncogene 2006 (Disease Progression...) : In these cells, the predominant effect of TRAIL receptor activation is the activation of nuclear factor-kappaB (NF-kappaB) , which promotes tumor metastases and invasion
Braeuer et al., Mol Cancer Res 2006 (Neoplasms) : We studied different cell lines displaying varying responses to TRAIL and found that TRAIL can activate NF-kappaB in all our cancer cell lines regardless of their TRAIL sensitivity
Ivanov et al., Exp Cell Res 2006 (Melanoma) : Furthermore, activation of cJun and suppression of NF-kappaB by sodium arsenite resulted in upregulation of the endogenous TRAIL and downregulation of the cFLIP gene expression ( which encodes one of the main anti-apoptotic proteins in melanomas ) followed by cFLIP protein degradation and, finally, by acceleration of TRAIL induced apoptosis
Kurbanov et al., Oncogene 2007 (Melanoma) : Here we show for the first time that TRAIL induced activation of NF-kappaB occurs in apoptosis-sensitive melanoma cell lines through TRAIL receptor 1/death receptor 4 ( TRAIL-R1/DR4 ), whereas TRAIL failed to activate nuclear factor kappa B (NF-kappaB) in melanoma cells positive only for TRAIL receptor 2/death receptor 5 ( TRAIL-R2/DR5 ) ... However, activation of NF-kappaB by TRAIL was not associated with enhanced expression of antiapoptotic factors : cellular FLICE-inhibitory protein ( c-FLIP ), Bcl-x ( L ), X-linked inhibitor of apoptosis protein ( XIAP ), Survivin, Livin
Hall et al., Cancer Cell 2007 (Neoplasms) : However, TRAIL signaling also activates NF-kappaB , which induces the antiapoptotic regulators Mcl-1 and cIAP2, thus compromising its efficacy
Ricci et al., Cancer Cell 2007 : TRAIL induced expression of antiapoptotic Mcl-1 and cIAP2 through activation of NF-kappaB
Wang et al., Cell Signal 2007 (Pancreatic Neoplasms) : Receptor interacting protein ( RIP ) has been reported in TRAIL induced activation of NF-kappaB and we show here that knockdown of RIP sensitized the resistant cells to TRAIL induced apoptosis
Ishiguro et al., Biochem Biophys Res Commun 2007 (Stomach Neoplasms) : 6-Gingerol was shown to down-regulate the expression of cIAP1, which suppresses caspase-3/7 activity, by inhibiting TRAIL induced NF-kappaB activation ... These findings indicate for the first time that in gastric cancer cells, 6-gingerol enhances TRAIL induced viability reduction by inhibiting TRAIL induced NF-kappaB activation while 6-shogaol alone reduces viability by damaging microtubules
Romagnoli et al., Clin Cancer Res 2007 (Multiple Myeloma) : Of particular interest, AS602868 strongly increased myeloma sensitivity to TRAIL in blocking TRAIL induced NF-kappaB activation and in decreasing the expression of antiapoptotic proteins such as cFLIP and cIAP-1/2
Diessenbacher et al., J Invest Dermatol 2008 : Although tumor necrosis factor (TNF) related apoptosis inducing ligand ( TRAIL ) and TNF both activate NF-kappaB in human keratinocytes, only TRAIL potently induces apoptosis
Lorz et al., J Am Soc Nephrol 2008 (Diabetic Nephropathies) : TRAIL also activated NF-kappaB , and inhibition of NF-kappaB sensitized cells to TRAIL induced apoptosis
Kallifatidis et al., Gut 2009 (Pancreatic Neoplasms) : Tumour necrosis factor related apoptosis inducing ligand ( TRAIL ) is considered to be a novel anticancer agent ; however, recent studies have shown that many pancreatic cancer cells are resistant to apoptosis induction by TRAIL due to TRAIL activated nuclear factor-kappaB (NF-kappaB) signalling
Kim et al., Biochem Biophys Res Commun 2008 (Astrocytoma) : In addition, TRAIL induces the DNA binding activity of NF-kappaB , an important transcription factor for MMP-9 induction ... The specific MEK inhibitor, U0126, significantly blocks TRAIL mediated NF-kappaB activation and subsequent MMP-9 induction
Klener et al., Blood Cells Mol Dis 2009 (Leukemia, Promyelocytic, Acute) : These resistant subclones had impaired activation of caspases 8 and 10 in response to TRAIL and TNFalpha, decreased TRAIL induced nuclear translocation of NFkappaB RelA/p65 , and dysregulation of the expression of several apoptosis regulators
Ammann et al., Int J Cancer 2009 (Neuroblastoma) : By comparison, inhibition of TRAIL stimulated NF-kappaB activation by IkappaBalpha-superrepressor or the small molecule NF-kappaB inhibitor BMS-345541 significantly enhances TRAIL induced apoptosis, pointing to an antiapoptotic function of NF-kappaB in TRAIL mediated apoptosis
Tanaka et al., Mol Cancer Res 2009 (Colonic Neoplasms...) : PRMT5 contributed to TRAIL induced activation of inhibitor of kappaB kinase (IKK) and nuclear factor-kappaB (NF-kappaB) , leading to induction of several NF-kappaB target genes
Bellail et al., J Cell Mol Med 2010 (Glioblastoma) : Treatment of resistant cells with parthenolide, an inhibitor of inhibitor of kappaB ( I-kappaB ), eliminated TRAIL induced NF-kappaB activity but not TRAIL resistance
Tang et al., Cell Res 2009 : TRAIL receptor mediates inflammatory cytokine release in an NF-kappaB dependent manner
Dai et al., BMC cancer 2009 (Prostatic Neoplasms) : SH122 also suppressed TRAIL induced NF-kappaB activation by preventing cytosolic IkappaB-alpha degradation and RelA nuclear translocation, as well as by suppressing NF-kappaB target gene expression
Kwon et al., Biochem Biophys Res Commun 2010 (Neoplasms) : Ablation of TOPK negatively regulated TRAIL mediated NF-kappaB activity
Lluis et al., PloS one 2010 : As well as causing apoptosis of certain types of tumor cells, TRAIL can activate both NF-kappaB and JNK signalling pathways
Chen et al., Molecular cancer 2010 (Carcinoma, Non-Small-Cell Lung...) : The combination of GGTI-298 and TRAIL was more effective than each single agent in decreasing the levels of IkappaBalpha and p-Akt, implying that GGTI298/TRAIL activates NF-kappaB and inhibits Akt
Chan et al., Circ Res 2010 : Furthermore, increased NFkappaB expression after injury transactivated the TRAIL promoter ... Conclusions : We conclude that TRAIL induction involves FGF-2, Sp1-phosphorylation and NFkappaB and that TRAIL promotes VSMC proliferation and neointima formation after arterial injury
Kim et al., Mol Cancer Ther 2010 (Carcinoma, Hepatocellular...) : In addition, ION significantly increased hepatocellular carcinoma cell sensitivity to TRAIL by abrogating TRAIL induced NF-kappaB activation and decreasing the expression of antiapoptotic proteins such as XIAP and IAP-1/2
Moon et al., Mol Cancer Ther 2010 (Carcinoma, Hepatocellular...) : Indeed, butein repressed the TRAIL mediated activation of NF-kappaB and decreased its transcriptional activity
Feng et al., Mol Immunol 2010 (Multiple Myeloma) : Pharmacological inhibition of the transcription factor, NF-kappaB also profoundly decreased TRAIL expression, suggesting that NF-kappaB is involved in the regulation of TRAIL expression in activated human NK cells
Lirdprapamongkol et al., In Vivo 2010 (Neoplasms...) : Vanillin pretreatment inhibited TRAIL induced phosphorylation of p65 and transcriptional activity of NF-kappaB
Fingas et al., Hepatology 2010 (Bile Duct Neoplasms...) : Treatment with JP1584 inhibited TRAIL induced NF-kappaB activation as well as TRAIL mediated up-regulation of the NF-kappaB target gene, matrix metalloproteinase 7 (MMP7)
Schneider et al., Immunity 1997 : TRAIL receptors 1 ( DR4 ) and 2 ( DR5 ) signal FADD dependent apoptosis and activate NF-kappaB
Jeremias et al., Blood 1998 : We demonstrate here that TRAIL ( TNF related apoptosis inducing ligand ), a recently identified DIL, also activates NFkappaB in lymphoid cell lines in a kinetic similar to TNFalpha
Jeremias et al., Eur Cytokine Netw 1998 : TRAIL induces apoptosis and activation of NFkappaB