Caspase-8 levels affect necessity for mitochondrial amplification in death ligand-induced glioma cell apoptosis.

Published

Journal Article

Fifty percent of high-grade glioma patients die within a year of diagnosis and less than two percent survive five years postdiagnosis. Elucidating apoptosis signaling pathways may assist in designing better adjuvant therapies. Preliminary characterizations suggested that glioma cells may either employ mitochondrial-independent or -dependent death receptor-induced apoptotic pathways, characteristic of cells termed type I and type II, respectively. In the present study, we generated panels of clonal transfectants overexpressing various levels of Bcl-2, in two parental glioma cell lines. These cells were used to explore molecular factors determining the necessity for mitochondrial amplification of death receptor signaling. Moderate Bcl-2 expression was sufficient to render one glioma cell line (D270) resistant to apoptosis induced by Fas ligand or TRAIL, consistent with these cells being type II. However, expression of even very high levels of Bcl-2 in a second line (D645) did not affect death ligand sensitivity, indicative of a type I phenotype. D270 cells expressed much less caspase-8 protein than D645 cells. Enforced overexpression of caspase-8 (or cytoplasmic Diablo/Smac) in D270 cells overcame Bcl-2 inhibition of death ligand-induced apoptosis, converting them from type II to type I. This indicates that caspase-8 levels can influence the requirement for mitochondrial involvement in death receptor apoptotic signaling in glioma cells.

Full Text

Duke Authors

Cited Authors

  • Knight, MJ; Riffkin, CD; Ekert, PG; Ashley, DM; Hawkins, CJ

Published Date

  • March 2004

Published In

Volume / Issue

  • 39 / 3

Start / End Page

  • 173 - 182

PubMed ID

  • 14991747

Pubmed Central ID

  • 14991747

International Standard Serial Number (ISSN)

  • 0899-1987

Digital Object Identifier (DOI)

  • 10.1002/mc.20011

Language

  • eng

Conference Location

  • United States