Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2001-09

AUTHORS

Melissa J Knight, Christopher D Riffkin, Andrea M Muscat, David M Ashley, Christine J Hawkins

ABSTRACT

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. More... »

PAGES

1204810

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1204810

DOI

http://dx.doi.org/10.1038/sj.onc.1204810

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1038375214

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11593384


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