scholarly journals Interferon-γ Sensitizes Resistant Ewing's Sarcoma Cells to Tumor Necrosis Factor Apoptosis-Inducing Ligand-Induced Apoptosis by Up-Regulation of Caspase-8 Without Altering Chemosensitivity

2007 ◽  
Vol 170 (6) ◽  
pp. 1917-1930 ◽  
Author(s):  
Andrej Lissat ◽  
Thomas Vraetz ◽  
Maria Tsokos ◽  
Ruth Klein ◽  
Matthias Braun ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Interferon Γ ◽  
Caspase 8 ◽  
Ewing's Sarcoma Cells ◽  
Induced Apoptosis ◽  
Sarcoma Cells ◽  
Necrosis Factor

scholarly journals Distinct Signaling Pathways in TRAIL- versus Tumor Necrosis Factor-Induced Apoptosis

2006 ◽  
Vol 26 (21) ◽  
pp. 8136-8148 ◽  
Author(s):  
Zhaoyu Jin ◽  
Wafik S. El-Deiry
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Human Tumor ◽  
Caspase 8 ◽  
Hairpin Rna ◽  
Complex Ii ◽  
Signaling Complex ◽  
Fas L ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT Trimeric tumor necrosis factor (TNF) binding leads to recruitment of TRADD to TNFR1. In current models, TRADD recruits RIP, TRAF2, and FADD to activate NF-κB, Jun N-terminal protein kinase (JNK), and apoptosis. Using stable short-hairpin RNA (shRNA) knockdown (KD) cells targeting these adaptors, TNF death-inducing signaling complex immunoprecipitation demonstrates competitive binding of TRADD and RIP to TNFR1, whereas TRAF2 recruitment requires TRADD. Analysis of KD cells indicates that FADD is necessary for Fas-L- or TRAIL- but not TNF-induced apoptosis. Interestingly, TRADD is dispensable, while RIP is required for TNF-induced apoptosis in human tumor cells. TRADD is required for c-Jun phosphorylation upon TNF exposure. RIP KD abrogates formation of complex II following TNF exposure, whereas TRADD KD allows efficient RIP-caspase 8 association. Treatment with TRAIL also induces formation of a complex II containing FADD, RIP, IKKα, and caspase 8 and 10, leading to activation of caspase 8. Our data suggest that TNF triggers apoptosis in a manner distinct from that of Fas-L or TRAIL.

Intracellular regulation of tumor necrosis factor–related apoptosis-inducing ligand–induced apoptosis in human multiple myeloma cells

Blood ◽  
2002 ◽  
Vol 99 (6) ◽  
pp. 2162-2171 ◽  
Author(s):  
Nicholas Mitsiades ◽  
Constantine S. Mitsiades ◽  
Vassiliki Poulaki ◽  
Kenneth C. Anderson ◽  
Steven P. Treon
Keyword(s):  
Multiple Myeloma ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Protein Synthesis Inhibitor ◽  
Caspase 8 ◽  
Data Set ◽  
Apoptosis Protein ◽  
Induced Apoptosis ◽  
Necrosis Factor ◽  
Resistant Cells

Abstract Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL, Apo2 ligand) effectively kills multiple myeloma (MM) cells in vitro irrespective of refractoriness to dexamethasone and chemotherapy. Because clinical trials with this anticancer agent are expected shortly, we investigated the signaling pathway of TRAIL-induced apoptosis in MM. We detected rapid cleavage of caspases-8, -9, -3, and -6, as well as the caspase substrates poly(ADP-ribose) polymerase (PARP) and DNA fragmentation factor-45 (DFF45), but not caspase-10, upon TRAIL treatment in sensitive MM cells, pointing to caspase-8 as the apical caspase of TRAIL signaling in MM cells. These phenomena were not observed or were significantly delayed in TRAIL-resistant MM cells, suggesting that resistance may arise from inhibition at the level of caspase-8 activation. Higher levels of expression for various apoptosis inhibitors, including FLICE-inhibitory protein (FLIP), and lower procaspase-8 levels were present in TRAIL-resistant cells and sensitivity was restored by the protein synthesis inhibitor cycloheximide (CHX) and the protein kinase C (PKC) inhibitor bisindolylmaleimide (BIM), which both lowered FLIP and cellular inhibitor of apoptosis protein-2 (cIAP-2) protein levels. Forced expression of procaspase-8 or FLIP antisense oligonucleotides also sensitized TRAIL-resistant cells to TRAIL. Moreover, the cell permeable nuclear factor (NF)–κB inhibitor SN50, which sensitizes TRAIL-resistant cells to TRAIL, also inhibited cIAP2 protein expression. Finally, CHX, BIM, and SN50 facilitated the cleavage and activation of procaspase-8 in TRAIL-resistant cells, confirming that inhibition of TRAIL-induced apoptosis occurs at this level and that these agents sensitize MM cells by relieving this block. Our data set a framework for the clinical use of approaches that sensitize MM cells to TRAIL by agents that inhibit FLIP and cIAP-2 expression or augment caspase-8 activity.

scholarly journals LIGHT, a Member of the Tumor Necrosis Factor Ligand Superfamily, Prevents Tumor Necrosis Factor-α-mediated Human Primary Hepatocyte Apoptosis, but Not Fas-mediated Apoptosis

2002 ◽  
Vol 277 (51) ◽  
pp. 50054-50061 ◽  
Author(s):  
Hideki Matsui ◽  
Yukiko Hikichi ◽  
Isamu Tsuji ◽  
Takao Yamada ◽  
Yasushi Shintani
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Time Course ◽  
Caspase 3 ◽  
Nuclear Factor Κb ◽  
Caspase 8 ◽  
Death Domain ◽  
Human Primary Hepatocytes ◽  
Induced Apoptosis ◽  
Necrosis Factor

LIGHT is a member of tumor necrosis factor (TNF) superfamily, and its receptors have been identified as lymphotoxin-β receptor (LTβR) and the herpesvirus entry mediator (HVEM)/ATAR/TR2, both of which lack the cytoplasmic sequence termed the “death domain.” The present study has demonstrated that LIGHT inhibits TNFα-mediated apoptosis of human primary hepatocytes sensitized by actinomycin D (ActD), but not Fas- or TRAIL-mediated apoptosis. Furthermore, LIGHT does not prevent some cell lines such as HepG2 or HeLa from undergoing ActD/TNFα-induced apoptosis. This protective effect requires LIGHT pretreatment at least 3 h prior to ActD sensitization. LIGHT stimulates nuclear factor-κB (NF-κB)-dependent transcriptional activity in human hepatocytes like TNFα. The time course of NF-κB activation after LIGHT administration is similar to that of the pretreatment required for the anti-apoptotic effect of LIGHT. LIGHT inhibits caspase-3 processing on the apoptotic protease cascade in TNFα-mediated apoptosis but not Fas-mediated apoptosis. In addition, increased caspase-3 and caspase-8 activities in ActD/TNFα-treated cells are effectively blocked by LIGHT pretreatment. However, LIGHT does not change the expression of TNFRp55, TNFRp75, and Fas. These results indicate that LIGHT may act as an anti-apoptotic agent against TNFα-mediated liver injury by blocking the activation of both caspase-3 and caspase-8.

scholarly journals Contrasting Effects of IG20 and Its Splice Isoforms, MADD and DENN-SV, on Tumor Necrosis Factor α-induced Apoptosis and Activation of Caspase-8 and -3

2001 ◽  
Vol 276 (50) ◽  
pp. 47202-47211 ◽  
Author(s):  
Adeeb M. Al-Zoubi ◽  
Elena V. Efimova ◽  
Shashi Kaithamana ◽  
Osvaldo Martinez ◽  
Mohammed El-Azami El-Idrissi ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Single Gene ◽  
Caspase 8 ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

We identified a novel cDNA (IG20) that is homologous to cDNAs encoding a proteindifferentiallyexpressed innormal andneoplastic cells (DENN-SV) and human MADD (MAPK-activatingdeathdomain-containing protein). Furthermore, we show that the above variants most likely result from alternative splicing of a single gene. Functional analyses of these variants in permanently transfected HeLa cells revealed that IG20 and DENN-SV render them more susceptible or resistant to tumor necrosis factor α (TNF-α)-induced apoptosis, respectively. All variants tested could interact with TNF receptor 1 and activate ERK and nuclear factor κB. However, relative to control cells, only cells expressing IG20 showed enhanced TNF-α-induced activation of caspase-8 and -3, whereas cells expressing DENN-SV showed either reduced or no caspase activation. Transfection of these cells with a cDNA encoding CrmA maximally inhibited apoptosis in HeLa-IG20 cells. Our results show that IG20 can promote TNF-α-induced apoptosis and activation of caspase-8 and -3 and suggest that it may play a novel role in the regulation of the pleiotropic effects of TNF-α through alternative splicing.

scholarly journals Hypericin photo-induced apoptosis involves the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and activation of caspase-8

FEBS Letters ◽  
2001 ◽  
Vol 493 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Christoph M Schempp ◽  
Birgit Simon-Haarhaus ◽  
Christian C Termeer ◽  
Jan C Simon
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Caspase 8 ◽  
Induced Apoptosis ◽  
Necrosis Factor

scholarly journals Caveolin-1 promotes resistance to chemotherapy-induced apoptosis in Ewing's sarcoma cells by modulating PKCα phosphorylation

2010 ◽  
Vol 126 (2) ◽  
pp. 426-436 ◽  
Author(s):  
Oscar M. Tirado ◽  
Caitlin M. MacCarthy ◽  
Naheed Fatima ◽  
Joaquín Villar ◽  
Silvia Mateo-Lozano ◽  
...  
Keyword(s):  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Caveolin 1 ◽  
Ewing's Sarcoma Cells ◽  
Induced Apoptosis ◽  
Sarcoma Cells ◽  
Resistance To Chemotherapy

scholarly journals Cytotoxicity of Tumor Necrosis Factor related apoptosis-inducing ligand towards Ewing's sarcoma cell lines

Oncogene ◽  
2001 ◽  
Vol 20 (8) ◽  
pp. 1010-1014 ◽  
Author(s):  
Arvind Kumar ◽  
Alan Jasmin ◽  
Michael T Eby ◽  
Preet M Chaudhary
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Lines ◽  
Tumor Necrosis ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Sarcoma Cell ◽  
Necrosis Factor
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