Premium
Erucylphosphocholine‐induced apoptosis in glioma cells: involvement of death receptor signalling and caspase activation
Author(s) -
Kugler Wilfried,
Erdlenbruch Bernhard,
Jünemann Anja,
Heinemann Dagmar,
Eibl Hansjörg,
Lakomek Max
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01034.x
Subject(s) - apoptosis , fadd , caspase , programmed cell death , glioma , caspase 8 , biology , cancer research , caspase 3 , tumor necrosis factor alpha , intrinsic apoptosis , necrosis , microbiology and biotechnology , immunology , biochemistry , genetics
Abstract Erucylphosphocholine (ErPC) is a promising anti‐neoplastic drug for the treatment of malignant brain tumours. It exerts strong anti‐cancer activity in vivo and in vitro and induces apoptosis even in chemoresistant glioma cell lines. The purpose of this study was to expand on our previous observations on the potential mechanisms of ErPC‐mediated apoptosis with a focus on death receptor activation and the caspase network. A172 and T98G glioma cells were treated with ErPC for up to 48 h. ErPC effects on the expression of the tumour necrosis factor (TNF) and TNF‐related apoptosis‐inducing ligand (TRAIL) receptor system, and on caspase activation were determined. ErPC had no effect on the expression of TNFα or TRAIL. Inhibition of the TNF or TRAIL signalling pathway with antagonistic antibodies or fusion proteins did not affect apoptosis induced by ErPC, and a dominant‐negative FADD construct did not abolish ErPC‐induced effects. Western blot analysis indicated that ErPC‐triggered apoptosis resulted in a time‐dependent processing of caspases‐3, ‐7, ‐8 and ‐9 into their respective active subunits. Co‐treatment of A172 cells with different caspase inhibitors prevented apoptosis but did not abrogate cell death. These data suggest that A172 cells might have an additional caspase‐independent pathway that insures cell death and guarantees killing of those tumour cells whose caspase pathway is incomplete.