Cytotoxicity mediated by tumor necrosis factor in variant subclones of the ME-180 cervical carcinoma line: Modulation by specific inhibitors of DNA topoisomerase II

1989 ◽  
Vol 39 (2) ◽  
pp. 95-105 ◽  
Author(s):  
Frederick D. Coffman ◽  
Lora M. Green ◽  
Angela Godwin ◽  
Carl F. Ware
Keyword(s):  
Tumor Necrosis Factor ◽  
Cervical Carcinoma ◽  
Tumor Necrosis ◽  
Topoisomerase Ii ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Necrosis Factor ◽  
Specific Inhibitors

scholarly journals Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Induces Caspase-Dependent Interleukin-8 Expression and Apoptosis in Human Astroglioma Cells

2002 ◽  
Vol 22 (3) ◽  
pp. 724-736 ◽  
Author(s):  
Chulhee Choi ◽  
Olaf Kutsch ◽  
Jinseu Park ◽  
Tong Zhou ◽  
Dai-Wu Seol ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Glioma Cells ◽  
Interleukin 8 ◽  
Human Glioma ◽  
Caspase Activation ◽  
Human Glioma Cells ◽  
Necrosis Factor ◽  
Specific Inhibitors

ABSTRACT Among the tumor necrosis factor (TNF) family of cytokines, FasL and TNF-related apoptosis-inducing ligand (TRAIL) are known to induce cell death via caspase activation. Recently, other biological functions of these death ligands have been postulated in vitro and in vivo. It was previously shown that Fas ligation induces chemokine expression in human glioma cells. In this study, we investigated whether the TRAIL-DR5 system transduces signals similar to those induced by other TNF family ligands and receptors. To address this issue, two human glioma cell lines, CRT-MG and U87-MG, were used, and an agonistic antibody against DR5 (TRA-8) and human recombinant TRAIL were used to ligate DR5. We demonstrate that DR5 ligation by either TRAIL or TRA-8 induces two functional outcomes, apoptosis and expression of the chemokine interleukin-8 (IL-8); the nonspecific caspase inhibitor Boc-D-Fmk blocks both TRAIL-mediated cell death and IL-8 production; the caspase 3-specific inhibitor z-DEVD-Fmk suppresses TRAIL-mediated apoptosis but not IL-8 induction; caspase 1- and 8-specific inhibitors block both TRAIL-mediated cell death and IL-8 production; and DR5 ligation by TRAIL mediates AP-1 and NF-κB activation, which can be inhibited by caspase 1- and 8-specific inhibitors. These findings collectively indicate that DR5 ligation on human glioma cells leads to apoptosis and that the activation of AP-1 and NF-κB leads to the induction of IL-8 expression; these responses are dependent on caspase activation. Therefore, the TRAIL-DR5 system has a role not only as an inducer of apoptotic cell death but also as a tranducer for proinflammatory and angiogenic signals in human brain tumors.

Sign in / Sign up

Export Citation Format

Share Document