Search results for "FAS ligand"
showing 10 items of 51 documents
Apoptosis induced by (E)-5-(2-bromovinyl)-2'-deoxyuridine in varicella zoster virus thymidine kinase-expressing cells is driven by activation of c-Ju…
2003
The molecular mode of cell killing by the antiviral drug (E)-5-(2-bromovinyl-2'-deoxyuridine (BVDU) was studied in Chinese hamster ovary (CHO) cells stably transfected with the thymidine kinase gene (tk) of varicella zoster virus (CHO-VZVtk). The colony-forming ability of the cells was reduced to <1% at a concentration of approximately 1 microM BVDU, whereas for nontransfected cells or cells transfected with tk gene of herpes simplex virus type 1 (CHO-HSVtk), a 1000-fold higher dose was required to achieve the same response. BVDU inhibited thymidylate synthase in CHO-VZVtk but not in CHO-HSVtk and control cells. On the other hand, the drug was incorporated into DNA of VZVtk- and HSVtk-expre…
Hyperthermia Enhances CD95-Ligand Gene Expression in T Lymphocytes
2004
Abstract Hyperthermia represents an interesting therapeutic strategy for the treatment of tumors. Moreover, it is able to regulate several aspects of the immune response. Fas (APO-1/CD95) and its ligand (FasL) are cell surface proteins whose interaction activates apoptosis of Fas-expressing targets. In T cells, the Fas-Fas-L system regulates activation-induced cell death, is implicated in diseases in which lymphocyte homeostasis is compromised, and plays an important role during cytotoxic and regulatory actions mediated by these cells. In this study we describe the effect of hyperthermia on activation of the fas-L gene in T lymphocytes. We show that hyperthermic treatment enhances Fas-L-med…
Response to 'Thyrocytes — not innocent bystanders in autoimmune disease'
2001
Giordano et al. propose that thyrocytes play a crucial role in the regulation of the autoimmune response during GD. According to them, Fas is weakly expressed in GD thyrocytes, whereas FasL is responsible for a specific deletion of infiltrating TH1 cells and maintains a TH2 phenotype in the lymphocytic infiltrate.
S-nitrosylation of the death receptor fas promotes fas ligand-mediated apoptosis in cancer cells.
2011
International audience; BACKGROUND & AIMS: Fas belongs to the family of tumor necrosis factor receptors which induce apoptosis. Many cancer cells express Fas but do not undergo Fas-mediated apoptosis. Nitric oxide reverses this resistance by increasing levels of Fas at the plasma membrane. We studied the mechanisms by which NO affects Fas function. METHODS: Colon and mammary cancer cell lines were incubated with the NO donor glyceryl trinitrate or lipid A; S-nitrosylation of Fas was monitored using the biotin switch assay. Fas constructs that contained mutations at cysteine residues that prevent S-nitrosylation were used to investigate the involvement of S-nitrosylation in Fas-mediated cell…
Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine
2006
Methylating drugs such as temozolomide (TMZ) are widely used in the treatment of brain tumours (malignant gliomas). The mechanism of TMZ-induced glioma cell death is unknown. Here, we show that malignant glioma cells undergo apoptosis following treatment with the methylating agents N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and TMZ. Cell death determined by colony formation and apoptosis following methylation is greatly stimulated by p53. Transfection experiments with O(6)-methylguanine-DNA methyltransferase (MGMT) and depletion of MGMT by O(6)-benzylguanine showed that, in gliomas, the apoptotic signal originates from O(6)-methylguanine (O(6)MeG) and that repair of O(6)MeG by MGMT prevent…
Pharmacogenomics of cantharidin in tumor cells.
2014
Cantharis vesicatoria (blister beetle) is used in Chinese medicine and has been categorized as highly toxic in the Chinese pharmacopeia. In Europe, Cantharis patches have been used since ages to treat various skin-related diseases. We investigated the cytotoxicity of the Cantharis ingredient, cantharidin, in 41 tumor cell lines (Oncotest panel) and compared the results with those of 60 cell lines of the National Cancer Institute, USA. We found profound activity at low micromolar concentrations (log ₁₀IC₅₀ values between -6.980 and 5.009 M). Cantharidin bound to protein phosphatase 2A (PP2A) with higher affinity (-8.12 kcal/mol) than to PP1 (-6.25 kcal/mol) in molecular docking analyses. Usi…
Deglycosylated bleomycin induces apoptosis in lymphoma cell via c-jun NH2-terminal kinase but not reactive oxygen species
2007
Bleomycin (BLM) has demonstrated potent activity in treating malignant lymphomas but its therapeutic efficacy is hampered by induction of lung fibrosis. This side effect is related to the ability of the drug to generate reactive oxygen species in lung cells. In the present study, we evaluated the consequences of deglycosylation of BLM in term of cytotoxic activity and generation of reactive oxygen species. When tested on U937 human lymphoma cells, both compounds generated a typical apoptotic phenotype. Cell death induction was associated with Bax oligomerization, dissipation of the mitochondrial membrane potential, release of cytochrome c, caspase activation, chromatin condensation and inte…
Role Of S-Nitrosylation In The Extrinsic Apoptotic Signalling Pathway In Cancer.
2015
One of the key features of tumour cells is the acquisition of resistance to apoptosis. Thus, determining therapeutic strategies that circumvent apoptotic resistance and result in tumor regression is a challenge. One strategy to induce apoptosis is to activate death receptor signalling pathways. Members of the Tumor Necrosis Factor TNF-family death receptors ligand (TRAIL, FasL and TNF-α) can originate from immune and non-immune cells. Death receptors, engaged by cognate ligands, can initiate multiple signaling pathways, which can generate diverse outcomes, including non-apoptosis-related signal. Knowledge on the molecular mechanisms (that determine death or survival of tumour cells) followi…
Apoptosis in liver disease
2001
A variety of biological functions are regulated through extracellular signals. Amongst the best studied examples is growth control, which is achieved by the regulatory function of growth factors. In recent years it has become apparent that cell death (apoptosis) is controlled in a similar fashion. Apoptosis, firstly a morphologically defined process, is a highly controlled type of cell death that plays a critical role in embryonic development, deletion of autoreactive T-cells and adult tissue homoeostasis. There is increasing evidence that derangement of the apoptotic program is the underlying cause of a series of diseases including liver diseases. The deadly program can be initiated by lig…
Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy--a study with monozygotic twin pairs.
2014
Biological aging is associated with physiological deteriorations and its’ remodeling, which are partly due to changes in the hormonal profile. MicroRNAs are known to post-transcriptionally regulate various cellular processes associated with cell senescence; differentiation, replication and apoptosis. Measured from the serum, microRNAs have the potential to serve as noninvasive markers for diagnostics/prognostics and therapeutic targets. We analysed the association of estrogen-based hormone replacement therapy (HRT) with selected microRNAs and inflammation markers from the serum, leukocytes and muscle tissue biopsy samples obtained from 54-62 year-old postmenopausal monozygotic twins (n=11 p…