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

Knight, Melissa J.; Riffkin, Christopher D.; Ekert, Paul G.; Ashley, David M.; Hawkins, Christine J.

doi:10.1002/mc.20011

Cited by 15 publications

(15 citation statements)

References 35 publications

(50 reference statements)

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“…When cells appeared to have reached 50% confluence or maximal confluency in a T25 flask for that cell line, they were expanded into a T75 flask (passage 2). Cells were also expanded into a T75 (passage 3) flask when they reached 50% (Knight et al, 2001(Knight et al, , 2004. LN18 cells were purchased from the ATCC (Manassas, VA, USA).…”

Section: Methodsmentioning

confidence: 99%

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

et al. 2008

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TRAIL/Apo-2L has shown promise as an anti-glioma drug, based on investigations of TRAIL sensitivity in established glioma cell lines, but it is not known how accurately TRAIL signalling pathways of glioma cells in vivo are reproduced in these cell lines in vitro. To replicate as closely as possible the in vivo behaviour of malignant glioma cells, 17 early passage glioma cell lines and 5 freshly resected gliomas were exposed to TRAIL-based agents and/or chemotherapeutic drugs. Normal human hepatocytes and astrocytes and established glioma cell lines were also tested. Cross-linked TRAIL, but not soluble TRAIL, killed both normal cell types and cells from three tumours. Cells from only one glioma were killed by soluble TRAIL, although only inefficiently. High concentrations of cisplatin were lethal to glioma cells, hepatocytes and astrocytes. Isolated combinations of TRAIL and chemotherapy drugs were more toxic to particular gliomas than normal cells, but no combination was generally selective for glioma cells. This study highlights the widespread resistance of glioma cells to TRAIL-based agents, but suggests that a minority of high-grade glioma patients may benefit from particular combinations of TRAIL and chemotherapy drugs. In vitro sensitivity assays may help identify effective drug combinations for individual glioma patients.

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Section: Methodsmentioning

confidence: 99%

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

et al. 2008

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“…Supernatant from the Neuro2A-CD95L cell line, containing active membrane-bound Fas ligand (FasL), was generated as described previously (21), as was supernatant from Neuro2A cells transfected with an empty vector (Neuro2A-neo). Lymphoblast and Jurkat cells ( ‫ف‬ 1 ϫ 10 6 cells) were resuspended in FasL supernatant plus various amounts of fresh medium to achieve different FasL dilutions and incubated for 24 h before analysis of cell viability by flow cytometry.…”

Section: Fas Ligand Induction Of Cell Deathmentioning

confidence: 99%

Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis

Valianpour

Mitsakos

Schlemmer

et al. 2005

Journal of Lipid Research

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130

140

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Barth syndrome (BTHS) is an X-linked recessive disorder that is biochemically characterized by low cellular levels of the mitochondrial phospholipid cardiolipin (CL). Previously, we discovered that the yeast disruptant of the TAZ ortholog in Saccharomyces cerevisiae not only displays CL deficiency but also accumulates monolysocardiolipins (MLCLs), which are intermediates in CL remodeling. Therefore, we set out to investigate whether MLCL accumulation also occurs in BTHS. Indeed, we observed MLCL accumulation in heart, muscle, lymphocytes, and cultured lymphoblasts of BTHS patients; however, only very low levels of these lysophospholipids were found in platelets and fibroblasts of these patients. Although the fatty acid composition of the MLCLs was different depending on the tissue source, it did parallel the fatty acid composition of the (remaining) CLs. The possible implications of these findings for the two reported CL remodeling mechanisms, transacylation and deacylation/ reacylation, are discussed. Because MLCLs have been proposed to be involved in the initiation of apoptosome-mediated cell death by the sequestration of the proapoptotic protein (t)BH3-interacting domain death agonist (Bid) to the mitochondrial membrane, we used control and BTHS lymphoblasts to investigate whether the accumulation of MLCLs results in higher levels of apoptosis. We found no differences in susceptibility to death receptor-mediated apoptosis or in cellular distribution of Bid, cytochrome c , and other parameters, implying that MLCL accumulation does not lead to enhanced apoptosis in cultured BTHS lymphoblasts. -Valianpour, F., V.

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“…76 Marked activation of death receptor-dependent apoptotic signals occurs in the context of mild cellular injury (type II cells). 77 Marked cellular damage results in activation of caspase-3, since caspase-8 can directly activate caspase-3 in the absence of mitochondrial pathway amplification (type I cells). 77 Thus, in type I cells caspase-3 becomes directly activated by caspase-8, whereas in type II cells caspase-3 activation involves activation of caspase-9 through the mitochondrial pathway.…”

Section: Intrinsic Apoptotic Pathway (Mitochondria-initiated Pathway)mentioning

confidence: 99%

The role of apoptosis in cancer cell survival and therapeutic outcome

Kim¹,

Emi²,

Tanabe³

2006

Cancer Biology & Therapy

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A number of discoveries have clarified the molecular mechanism of apoptosis, thus clarifying the link between apoptosis and therapeutic outcome. Even though apoptosis is thought to play a major role in anticancer therapy, the clinical relevance of induction of apoptosis remains uncertain, particularly in solid tumors. Induction of apoptosis by anticancer agents has been shown to correlate with tumor response, however, non-apoptotic forms of cell death, such as autophagy and extrinsic senescence, have also been shown to contribute to the overall tumor response. Cellular damage induces growth arrest and tumor suppression by inducing apoptosis, necrosis, and senescence; the mechanism of cell death depends on the magnitude of DNA damage following exposure to various concentrations of anticancer agents. Apoptosis-resistant cells and transduction pathways which inhibit apoptosis can induce non-apoptotic mechanisms of cell death and senescence, thereby preserving the antitumor effect of some anticancer agents. Heterogeneic antitumor responses include various cell types of cell death, depending on the degree of cellular or DNA damage incurred by cancer cells. As a new therapeutic strategy, alternative types of cell death might be exploited to control and eradicate cancer cells. This review discusses the clinical significance of apoptosis, as well as the potential contribution of other types of cell death to overall tumor sensitivity in the hopes that new therapeutic strategies might follow.

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

Cited by 15 publications

References 35 publications

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis

The role of apoptosis in cancer cell survival and therapeutic outcome

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