TRAIL Triggers Apoptosis in Human Malignant Glioma Cells Through Extrinsic and Intrinsic Pathways
作者： Jin H. Song , Doyoun K. Song , Beata Pyrzynska , Kenneth C. Petruk , Erwin G. Meir
DOI: 10.1111/J.1750-3639.2003.TB00484.X
关键词:
摘要: Many malignant glioma cells express death receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), yet some of these are resistant to TRAIL. Here, we examined signaling events in TRAIL-induced apoptosis and searched therapeutic agents that could overcome TRAIL resistance cells. induced through receptor 5 (DR5) was mediated by caspase-8-initiated extrinsic intrinsic mitochondrial pathways sensitive cell lines. also triggered lines the same pathways, but only if were pretreated with chemotherapeutic agents, cisplatin, camptothecin etoposide. Previous studies suggested this due an increase DR5 expression wild-type TP53 cells, mechanism did not account mutant TP53. show a more general effect is downregulate caspase-8 inhibitor c-FLIP(S) (the short form cellular Fas-associated domain-fike interleukin-1-converting enzyme-inhibitory protein) up-regulate Bak, pro-apoptotic Bcl-2 family member, independently cell's status. Furthermore, showed alone or combination primary cultures from patients gliomas, reinforcing potential as effective agent gliomas.
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