Caspase-1 Mediates Fas-Induced Apoptosis and is Up-Regulated by Interferon-  in Human Astrocytoma Cells

Choi, Chulhee; Jeong, Eun-Joo; Benveniste, Etty N.

doi:10.1023/b:neon.0000021896.52664.9e

Cited by 22 publications

(9 citation statements)

References 43 publications

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“…19 Caspase-1 is involved in Fas-induced apoptosis, although this route is not so well characterized. 20,21 In addition, caspase-4 may also mediate Fas-induced …”

Section: Discussionmentioning

confidence: 99%

TIMP‐3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway

Kallio

Hopkins-Donaldson

Baker

et al. 2010

Intl Journal of Cancer

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Tissue inhibitor of metalloproteinases-3 (TIMP-3) has previously been identified as a tumor suppressor for adherent malignant and normal cells. TIMP-3 inhibits adhesion of cells to extracellular matrix and promotes apoptosis through death receptoractivated, caspase-8-mediated pathway. Here, we have studied the effect of adenovirally mediated overexpression of TIMP-3 on small cell lung cancer (SCLC) cell lines SW2 and N417, which grow in suspension and lack functional caspase-8. The results show that adenoviral delivery of TIMP-3 promotes apoptotic cell death in SCLC cells in the absence of caspase-8 activation. These results suggest TIMP-3 as a promising therapeutic anticancer protein also in nonadherent malignant cells lacking functional death receptor signaling.Proteolytic turnover of basement membrane and extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is an important event in tumor growth, invasion and metastasis.

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“…19 Caspase-1 is involved in Fas-induced apoptosis, although this route is not so well characterized. 20,21 In addition, caspase-4 may also mediate Fas-induced …”

Section: Discussionmentioning

confidence: 99%

TIMP‐3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway

Kallio

Hopkins-Donaldson

Baker

et al. 2010

Intl Journal of Cancer

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“…To test the effect of C-K on Fas-mediated cell death, the CRT-MG cells were incubated in the absence or the presence of varying concentrations of C-K for 1 h and then the cells were treated with increasing doses of CH-11 anti-Fas antibody for 24 h. As CRT-MG cells are known to be resistant to Fas-induced cell death (16), the cells did not undergo cell death upon Fas ligation in the absence of C-K (Fig. 4A).…”

Section: The Synergistic Effect Of Ginsenosides On Fas-induced Cell Dmentioning

confidence: 99%

Proapoptotic Ginsenosides Compound K and Rh2 Enhance Fas-induced Cell Death of Human Astrocytoma Cells Through Distinct Apoptotic Signaling Pathways

Choi

2009

Cancer Res Treat

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I n t r o d u c t i o nGlioblastoma multiforme (GBM) is the most malignant and common brain tumor and it comprises ~23% of all primary brain tumors in adults. These malignancies are refractory to all the current therapeutic approaches, including surgery, radiotherapy and chemotherapy. Fas (CD95 or APO-1) is a member of the TNF/NGF receptor family, and Fas induces caspase-dependent apoptotic death in various transformed cells (1,2). Fas ligation with natural ligand or agonistic anti-Fas antibody is followed by recruitment of proapoptotic adaptor molecules such as Fas-associated death domain (FADD) to transduce the apoptotic signals through the caspase cascades (3). In some cells, Fas efficiently activates caspase-8 and it subsequently activates caspase-3 or 7, while other types of Fasinduced apoptosis are mediated by cytochrome-C release from the mitochondria and this is inhibited by the over-expression of antiapoptotic bcl-2 family members (4).Panax Ginseng is known for its biological and pharmacological activities such as its anti-cancer, anti-aging, anti-inflammatory and anti-oxidant properties in the nervous, immune and circulatory systems (5). These diverse physiological activities of ginseng are mainly mediated by saponin, which is a ginsenoside. Especially, the metabolites of ginsenosides that are formed by enteric bacteria have been focused on for their pharmacological activities. Among them, compound K (C-K) is known to be formed by enteric bacterial fermentation of Rb1, Rb2 and RC, and C-K has been reported to suppress tumor metastasis and inflammatory responses (6,7). Another ginsenoside Rh2, a metabolite of Rg3, is also known for its tumor suppression by inducing apoptosis or retarding growth signals (8).We have previously shown that human malignant astrocytoma cells are quite resistant to Fas-induced apoptosis even though these Cancer Res Treat. 2009;41(1):36-44 Purpose Malignant astrocytomas are among the commonest primary brain tumors and they have a grave prognosis, and so there is an urgent need to develop effective treatment. In this study, we investigated the molecular mechanisms that are responsible for the anti-tumor effect of ginsenosides on human astrocytoma cells. Materials and MethodsWe tested 13 different ginsenosides for their anti-tumor effect on human malignant astrocytoma cells in conjunction with Fas stimulation. In addition, the cell signaling pathways were explored by using pharmacological inhibitors and performing immunoblot analysis. DCF-DA staining and antioxidant experiments were performed to investigate the role of reactive oxygen species as one of the apoptosis-inducing mechanisms. ResultsAmong the 13 different ginsenoside metabolites, compound K and Rh2 induced apoptotic cell death of the astrocytoma cells in a caspase-and p38 MAPK-dependent manner, yet the same treatment had no cytotoxic effect on the primary cultured human astrocytes. Combined treatment with ginsenosides and Fas ligand showed a synergistic cytotoxic effect, which was mediated by the reduction of intracell...

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“…For example, tumor necrosis factor alpha (TNFα) can show enhanced cytotoxicity in oligodendrocytes and transformed human neural cell lines when co-exposed with IFNγ. 3,[10][11][12][13][14][15][16][17][18][19] In contrast with reported toxic effects of IFNγ on oligodendrocytes, other studies did not see negative effects on mature oligodendrocytes 5,9,20 or saw protection of glial lineage cells. IFNγ protects the Oli-neu oligodendrocyte-like cell line from reactive oxygen and nitrogen species, 21 and overexpression of IFNγ before the induction of experimental autoimmune encephalomyelitis (EAE) protected oligodendrocytes from immune-mediated damage.…”

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confidence: 83%

cFLIP is critical for oligodendrocyte protection from inflammation

et al. 2015

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Neuroinflammation associated with degenerative central nervous system disease and injury frequently results in oligodendrocyte death. While promoting oligodendrocyte viability is a major therapeutic goal, little is known about protective signaling strategies. We report that in highly purified rat oligodendrocytes, interferon gamma (IFNγ) activates a signaling pathway that protects these cells from tumor necrosis factor alpha (TNFα)-induced cytotoxicity. IFNγ protection requires Jak (Janus kinase) activation, components of the integrated stress response and NF-κB activation. Although NF-κB activation also occurred transiently in the absence of IFNγ and presence of TNFα, this activation was not sufficient to prevent induction of the TNFα-responsive cell death pathway. Genetic inhibition of NF-κB translocation to the nucleus abrogated IFNγ-mediated protection and did not change the cell death induced by TNFα, suggesting that NF-κB activation via IFNγ induces a different set of responses than activation of NF-κB via TNFα. A promising candidate is the NF-κB target cFLIP (cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein), which is protease-deficient caspase homolog that inhibits caspase-3 activation. We show that IFNγ-mediated protection led to upregulation of cFLIP. Overexpression of cFLIP was sufficient for oligodendrocyte protection from TNFα and short hairpin RNA knockdown of cFLIP-abrogated IFNγ -mediated protection. To determine the relevance of our in vitro finding to the more complex in vivo situation, we determined the impact on oligodendrocyte death of regional cFLIP loss of function in a murine model of neuroinflammation. Our data show that downregulation of cFLIP during inflammation leads to death of oligodendrocytes and decrease of myelin in vivo. Taken together, we show that IFNγ-mediated induction of cFLIP expression provides a new mechanism by which this cytokine can protect oligodendrocytes from TNFα-induced cell death.

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Caspase-1 Mediates Fas-Induced Apoptosis and is Up-Regulated by Interferon- in Human Astrocytoma Cells

Cited by 22 publications

References 43 publications

TIMP‐3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway

TIMP‐3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway

Proapoptotic Ginsenosides Compound K and Rh2 Enhance Fas-induced Cell Death of Human Astrocytoma Cells Through Distinct Apoptotic Signaling Pathways

cFLIP is critical for oligodendrocyte protection from inflammation

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