Search results for "Cell death"
showing 10 items of 824 documents
Cytotoxicity of ungeremine towards multi-factorial drug resistant cancer cells and induction of apoptosis, ferroptosis, necroptosis and autophagy
2018
Abstract Background Successful cancer chemotherapy is hampered by resistance of cancer cells to established anticancer drugs. Numerous natural products reveal cytotoxicity towards tumor cells. Purpose The present study was aimed to determine the cytotoxicity of a betaine-type alkaloid, ungeremine, towards 9 cancer cell lines including various sensitive and drug-resistant phenotypes. The mode of action of this compound was further investigated. Methods The cytotoxicity, ferroptotic and necroptotic cell death were determined by the resazurin reduction assay. Caspase activation was evaluated using the caspase-Glo assay. Flow cytometry was applied for the analysis of cell cycle analysis (PI sta…
Apoptosis of T cells and the control of inflammatory bowel disease: therapeutic implications.
2007
Inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis are the result of an imbalanced mucosal T cell response. Despite the identification of a genetic susceptibility region in the NOD2/CARD15 (nucleotide-binding oligomerisation domain 2/caspase recruitment domain 15) gene, the aetiology is still unclear. Thus, the hunt for disease-initiating factors such as defects in the mucosal barrier or pathogenic microorganisms is ongoing. By contrast, the immunopathogenesis in IBDs is better understood. The identification of cytokines that are involved in T cell and monocyte signalling led to specific therapeutic concepts. Recent data have clearly shown that the most powerf…
Size-Dependent Oxygenation and Energy Status in Multicellular Tumor Spheroids
1990
Multicellular tumor spheroids show numerous analogies to tumor microregions in vivo, such as the development of central necrosis at a certain spheroid size (for reviews see: Mueller-Klieser, 1987; Sutherland, 1988). The histological structure of the cell aggregates suggests that diffusion limitation of oxygen or nutrients in spheroids may cause cell death in the innermost parts of the spheroids. However, measurements with oxygen-sensitive microelectrodes are indicative of necrosis arising in the presence of relatively high oxygen tension (PO2) values, as they were found in normal tissue (Carlsson and Acker, 1985; Mueller-Klieser et al., 1986). Although still controversial in literature, rec…
Differential Roles of JNK in ConA/GalN and ConA-Induced Liver Injury in Mice
2008
Tumor necrosis factor-alpha-mediated liver injury can be induced by several different means; however, the signaling events and mechanisms of cell death are likely different. We investigated the mechanism of both apoptotic and necrotic hepatocyte cell death as well as the role of c-Jun NH2-terminal kinase (JNK) in the ConA and ConA/D-galactosamine (GalN) models of murine liver injury. ConA alone induced primarily necrotic cell death with no caspase activation, whereas ConA/GalN induced apoptosis in addition to necrotic cell death. The bi-modal death pattern in the ConA/GalN model was confirmed by the use of transgenic mice expressing a dominant-negative form of Fas-associated death domain in…
Hepassocin as a treatment for fulminant hepatic failure: will it translate from rats to human?
2010
Acute liver failure (ALF) is defined as the abrupt loss of hepatic cellular function in a patient without pre-existing liver disease, with the subsequent development of coagulopathy, jaundice and encephalopathy. It remains one of the most challenging medical emergencies, due to the multiorgan nature of the disease, the rapid evolution of the clinical condition and the need for multidisciplinary supportive interventions in order to assess the necessity for liver transplantation (LT) correctly.1 Despite different causes of ALF, the mode of cell death typically follows one of two patterns: necrosis or apoptosis; apoptosis is manifest by nuclear and cytoplasmic shrinkage without disturbance of …
Studies on the apoptotic activity of natural and synthetic retinoids: discovery of a new class of synthetic terphenyls that potently support cell gro…
2005
New terphenyl derivatives have been synthesized and tested for their effect on cell survival in serum-free cultures. These compounds protected HL60 cells from death and supported their growth with an activity higher than that of the natural 14-hydroxy-retro-retinol. Terphenyls 26 and 28 also possess antiapoptotic activity on neuronal cells, proving them as possible candidates for the treatment of neurodegenerative and ischemic diseases.
Prevention of 7-ketocholesterol-induced side effects by natural compounds
2018
Cholesterol oxidation products, also named oxysterols, can be formed either by cholesterol auto-oxidation, enzymatically or both. Among these oxysterols, 7-ketocholesterol (7KC) is mainly formed during radical attacks that take place on the carbon 7 of cholesterol. As increased levels of 7KC have been found in the tissues, plasma and/or cerebrospinal fluid of patients with major diseases, especially age-related diseases (cardiovascular diseases, eye diseases, neurodegenerative diseases), some cancers, and chronic inflammatory diseases, it is suspected that 7KC, could contribute to their development. Since 7KC, provided by the diet or endogenously formed, is not or little efficiently metabol…
Absence of correlation between oxysterol accumulation in lipid raft microdomains, calcium increase, and apoptosis induction on 158N murine oligodendr…
2013
There is some evidence that oxidized derivatives of cholesterol, 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7βOHC), are increased in the plasma of patients with neurodegenerative diseases associated with demyelinization of the central nervous system (CNS). It was therefore of interest to investigate the effects of these oxysterols on oligodendrocytes, the myelin-forming cells in the CNS. To this end, 158N murine oligodendrocytes were treated with 7KC or 7βOHC inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl-1, and caspase-3 activation. In contrast, under t…
Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-ind…
2007
International audience; Among the oxysterols accumulating in atherosclerotic plaque, 7-ketocholesterol (7KC) is a potent apoptotic inducer, which favours myelin figure formation and polar lipid accumulation. This investigation performed on U937 cells consisted in characterizing the myelin figure formation process; determining the effects of 7KC on the PI3-K/PDK-1/Akt signalling pathway; evaluating the activities of vitamin E (Vit-E) (α-tocopherol) on the formation of myelin figures and the PI3-K/PDK-1/Akt signalling pathway and assessing the effects of PI3-K inhibitors (LY-294002, 3-methyladenine) on the activity of Vit-E on cell death and polar lipid accumulation. The ultrastructural and b…
Absence of oxysterol-like side effects in human monocytic cells treated with phytosterols and oxyphytosterols
2012
Oxysterols, found in some commonly consumed foods, can induce a wide range of cytotoxic effects, which have been extensively studied. On the other hand, the side effects of phytosterols and oxyphytosterols are less well-known. Over the past few years, different types of foods have been enriched with phytosterols on the basis of the properties of these compounds that reduce circulating cholesterol levels in certain experimental conditions. It is therefore important to gain better knowledge of the risks and benefits of this type of diet. In this study, conducted in human monocytic U937 cells, the ability of phytosterols (sitosterol, campesterol) and oxyphytosterols (7 beta-hydroxysitosterol, …