Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells.

Published

Journal Article

FasL and TNF-related apoptosis-inducing ligand (TRAIL) belong to a subgroup of the TNF superfamily which induce apoptosis by binding to their death domain containing receptors. In the present study we have utilized a panel of seven cell lines derived from human malignant gliomas to characterize molecular pathways through which FasL and TRAIL induce apoptosis in sensitive glioma cells and the mechanisms of resistance in cell lines which survive the death stimuli. Our findings indicate that FADD and Caspase-8 are essential for FasL and TRAIL mediated apoptosis in glioma cells. One sensitive cell line (D270) can be protected from FasL and TRAIL induced death by anti-apoptotic Bcl-2 family members while another (D645) cannot, implying that these lines may represent glioma examples of type II and type I cells respectively. For the first time we demonstrate resistance to FasL but not to TRAIL within the one glioma cell line. Furthermore, we report distinct mechanisms of resistance within different glioma lines, including downregulation of Caspase-8 in U373MG. Cycloheximide sensitized four of the resistant cell lines suggesting the presence of labile inhibitors. None of the known apoptosis inhibitors examined accounted for the observed resistance, suggesting novel inhibitors may exist in glioma cells.

Full Text

Duke Authors

Cited Authors

  • Knight, MJ; Riffkin, CD; Muscat, AM; Ashley, DM; Hawkins, CJ

Published Date

  • September 13, 2001

Published In

Volume / Issue

  • 20 / 41

Start / End Page

  • 5789 - 5798

PubMed ID

  • 11593384

Pubmed Central ID

  • 11593384

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1204810

Language

  • eng

Conference Location

  • England