Search results for "Programmed cell death"
showing 10 items of 609 documents
Combined inhibition of Bcl-2 and NFκB synergistically induces cell death in cutaneous T-cell lymphoma.
2019
Abstract Therapeutic options for cutaneous T-cell lymphoma (CTCL) are limited and curative treatment regimens are not available. Thus, new targeted and well-tolerated therapeutic approaches are urgently needed. In this respect, we have recently shown that dimethyl fumerate (DMF) inhibits NF-κB acting as a survival factor in CTCL. Similarly, inhibition of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) has been shown to induce cell death in CTCL especially when combined with histone deacetylase inhibitors. Therefore, we hypothesized that inhibition of Bcl-2 should potentiate NF-κB inhibition in a novel combination treatment of CTCL. We show that, in vitro, the Bcl-2 inhibitors ABT-199 an…
Coupling Endoplasmic Reticulum Stress to the Cell Death Program
2002
Accumulation of misfolded proteins and alterations in Ca2+ homeostasis in the endoplasmic reticulum (ER) causes ER stress and leads to cell death. However, the signal-transducing events that connect ER stress to cell death pathways are incompletely understood. To discern the pathway by which ER stress-induced cell death proceeds, we performed studies on Apaf-1−/− (null) fibroblasts that are known to be relatively resistant to apoptotic insults that induce the intrinsic apoptotic pathway. While these cells were resistant to cell death initiated by proapoptotic stimuli such as tamoxifen, they were susceptible to apoptosis induced by thapsigargin and brefeldin-A, both of which induce ER stress…
Selective loss of regulatory T cells in thymomas
2004
Myasthenia gravis (MG) is the prime autoimmune manifestation of thymomas. We investigated the generation of T cells with a regulatory phenotype (T(R)) in thymomas with and without associated MG. In patients with MG(+) thymomas, maturation and export of T(R) cells but not of other T-cell subsets was significantly reduced. We conclude that imbalance between effector and regulatory T cells in thymomas may be involved in modulation of onset and/or severity of MG.
Coffee Silverskin and Spent Coffee Suitable as Neuroprotectors against Cell Death by Beauvericin and α-Zearalenol: Evaluating Strategies of Treatment
2021
Coffee silverskin and spent coffee have been evaluated in a neuroblastoma cell line (SH-SY5Y cells) against beauvericin (BEA) and α-zearalenol (α-ZEL)-induced cytotoxicity with different strategies of treatment. First, the direct treatment of mycotoxins and coffee by-products extracts in SH-SY5Y cells was assayed. IC50 values for α-ZEL were 20.8 and 14.0 µM for 48 h and 72 h, respectively and, for BEA only at 72 h, it was 2.5 µM. Afterwards, the pre-treatment with spent coffee obtained by boiling water increased cell viability for α-ZEL at 24 h and 48 h from 10% to 16% and from 25% to 30%, respectively
Macrophage-mediated clearance of cells undergoing caspase-3-independent death
2003
Little is known of the functions of caspases in mediating the surface changes required for phagocytosis of dying cells. Here we investigate the role played by the effector caspase, caspase-3 in this process using the caspase-3-defective MCF-7 breast carcinoma line and derived caspase-3-expressing transfectants. Our results indicate that, while certain typical features of apoptosis induced by etoposide - namely classical morphological changes and the ability to degrade DNA into oligonucleosomal fragments - are caspase-3-dependent, loss of cell adhesion to plastic and the capacity to interact with, and to be phagocytosed by, human monocyte-derived macrophages - both by CD14-dependent and CD14…
α-Tocopherol impairs 7-ketocholesterol-induced caspase-3-dependent apoptosis involving GSK-3 activation and Mcl-1 degradation on 158N murine oligoden…
2011
Abstract In important and severe neurodegenerative pathologies, 7-ketocholesterol, mainly resulting from cholesterol autoxidation, may contribute to dys- or demyelination processes. On various cell types, 7-ketocholesterol has often been shown to induce a complex mode of cell death by apoptosis associated with phospholipidosis. On 158N murine oligodendrocytes treated with 7-ketocholesterol (20 μg/mL corresponding to 50 μM, 24–48 h), the induction of a mode of cell death by apoptosis characterised by the occurrence of cells with condensed and/or fragmented nuclei, caspase activation (including caspase-3) and internucleosomal DNA fragmentation was observed. It was associated with a loss of tr…
Effect of ultraviolet light, methyl methanesulfonate and ionizing radiation on the genotoxic response and apoptosis of mouse fibroblasts lacking c-Fo…
2001
c-Fos and p53 are DNA damage-inducible proteins that are involved in gene regulation, cell cycle checkpoint control and cell proliferation following exposure to genotoxic agents. To investigate comparatively the role of c-Fos and p53 in the maintenance of genomic stability and the induction of apoptosis, we generated mouse fibroblast cell lines from knockout mice deficient for either c-fos (fos -/-) or p53 (p53-/-) or for both gene products (fosp53-/-). The sensitivity of these established cell lines was compared with the corresponding wild-type cells as to the cytotoxic, clastogenic and apoptosis-inducing effects of ultraviolet (UV-C) light and methyl methanesulfonate (MMS). Additionally, …
Cisplatin-induced apoptosis in 43-3B and 27-1 cells defective in nucleotide excision repair
2001
Cisplatin is a highly potent cytotoxic and genotoxic agent used in the chemotherapy of various types of tumors. Its cytotoxic effect is supposed to be due to the induction of intra- and interstrand DNA cross-links which are repaired via the nucleotide excision repair (NER) pathway. Here, we elucidated the mechanism of cisplatin-induced cytotoxicity in mutants derived from CHO-9 cells defective in NER. We compared 43-3B and 27-1 cells deficient for ERCC1 and ERCC3, respectively, with the corresponding wild-type and ERCC1 complemented 43-3B cells. It is shown that cells defective in ERCC1 are more sensitive than cells defective in ERCC3 with regard to cisplatin-induced reproductive cell death…
Apoptotic Activities of Mediterranean Plant Species
2015
Abstract Throughout the Mediterranean region, medicinal plants are widely used to improve health and avoid disease. Various epidemiological studies indicate that some of these plants reduce the incidence of inflammatory diseases and cancer by inducing programmed cell death, thus arresting proliferation. Several of these plant species, including saffron, capsicum, garlic, and onion, are employed for many purposes, while others, such as mistletoe, myrtle, French lavender, and rue, have more selective uses. For example, saffron exerts a chemopreventive effect by inhibiting cell proliferation and inducing apoptosis, and garlic inhibits cancer cell growth by promoting early mitotic arrest and ap…
MYC and EGR1 synergize to trigger tumor cell death by controlling NOXA and BIM transcription upon treatment with the proteasome inhibitor bortezomib
2014
The c-MYC (MYC afterward) oncogene is well known for driving numerous oncogenic programs. However, MYC can also induce apoptosis and this function of MYC warrants further clarification. We report here that a clinically relevant proteasome inhibitor significantly increases MYC protein levels and that endogenous MYC is necessary for the induction of apoptosis. This kind of MYC-induced cell death is mediated by enhanced expression of the pro-apoptotic BCL2 family members NOXA and BIM. Quantitative promoter-scanning chromatin immunoprecipitations (qChIP) further revealed binding of MYC to the promoters of NOXA and BIM upon proteasome inhibition, correlating with increased transcription. Both pr…