Search results for " STRESS"
showing 10 items of 3936 documents
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…
Targeting the mitochondrial pathway to induce apoptosis/necrosis through ROS by a newly developed Schiff’s base to overcome MDR in cancer
2011
Abstract Multidrug resistance (MDR) in cancer, a major obstacle to successful application of cancer chemotherapy, is often characterized by over-expression of multidrug resistance-related proteins such as MRP1, P-gp or elevated glutathione (GSH) level. Efflux of drugs by functional P-gp, MRP1 and elevated GSH level can confer resistance to apoptosis induced by a range of different stimuli. Therefore, it is necessary to develop new cell death inducers with relatively lower toxicity toward non-malignant cells that can overcome MDR by induction of apoptotic or non-apoptotic cell death pathways. Herein we report the synthesis and spectroscopic characterization of a GSH depleting, redox active S…
Induction of oxiapoptophagy, a mixed mode of cell death associated with oxidative stress, apoptosis and autophagy, on 7-ketocholesterol-treated 158N …
2013
7-Ketocholesterol (7KC) has been suggested to induce a complex mode of cell death on monocytic cells: oxiapoptophagy (OXIdation, APOPTOsis, and autoPHAGY) (Monier et al. (2003) [12]). The aim of the present study, realized on 158N murine oligodendrocytes, was to bring new evidence on this mixed form of cell death. On 158N cells, 7KC induces an overproduction of reactive oxygen species (ROS) revealed by dihydroethidium staining, a loss of transmembrane mitochondrial potential measured with DiOC6(3), caspase-3 activation, and condensation and/or fragmentation of the nuclei which are typical criteria of oxidative stress and apoptosis. Moreover, 7KC enhances cytoplamic membrane permeability to …
Targeting Mitochondria: A New Promising Approach for the Treatment of Liver Diseases
2010
Mitochondrial dysfunction acts as a common pathogenetic mechanism in several acute and chronic liver diseases, such as Alcoholic and Non-Alcoholic Fatty Liver Disease (NAFLD), drug-induced steatohepatitis, viral hepatitis, biliary cirrhosis, hepatocellular carcinoma, ischemia/reperfusion injury and transplant rejection. In particular mitochondrial uncoupling has been recently identified to play a determinant role in the pathogenesis of liver diseases by causing decrease of mitochondrial proton motive force and ATP depletion. Damaged mitochondria present defects in lipid homeostasis, bioenergetics impairment and overproduction of Reactive Oxygen Species (ROS), leading to lipid accumulation a…
ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells
2020
Organotin compounds represent potential cancer therapeutics due to their pro-apoptotic action. We recently synthesized the novel organotin ferulic acid derivative tributyltin (IV) ferulate (TBT-F) and demonstrated that it displays anti-tumor properties in colon cancer cells related with autophagic cell death. The purpose of the present study was to elucidate the mechanism of TBT-F action in colon cancer cells. We specifically show that TBT-F-dependent autophagy is determined by a rapid generation of reactive oxygen species (ROS) and correlated with endoplasmic reticulum (ER) stress. TBT-F evoked nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant response and Nrf2 silenc…
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…
Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection
2020
Neurodegenerative diseases, particularly Parkinson’s and Alzheimer’s, have common features: protein accumulation, cell death with mitochondrial involvement and oxidative stress. Patients are treated to cure the symptoms, but the treatments do not target the causes; so, the disease is not stopped. It is interesting to look at the side of nutrition which could help prevent the first signs of the disease or slow its progression in addition to existing therapeutic strategies. Lipids, whether in the form of vegetable or animal oils or in the form of fatty acids, could be incorporated into diets with the aim of preventing neurodegenerative diseases. These different lipids can inhibit the cytotoxi…
A high-throughput chemical screen in DJ-1β mutant flies identifies zaprinast as a potential Parkinson's disease treatment
2021
AbstractDopamine replacement represents the standard therapy for Parkinson’s disease (PD), a common, chronic, and incurable neurological disorder; however, this approach only treats the symptoms of this devastating disease. In the search for novel disease-modifying therapies that target other relevant molecular and cellular mechanisms, Drosophila has emerged as a valuable tool to study neurodegenerative diseases due to the presence of a complex central nervous system, the blood–brain barrier, and a similar neurotransmitter profile to humans. Human PD-related genes also display conservation in flies; DJ-1β is the fly ortholog of DJ-1, a gene for which mutations prompt early-onset recessive P…
Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca(2+) increase and oxidative stress.
2012
7-Ketocholesterol (7-KC)-induced apoptosis of macrophages is considered a key event in the development of human atheromas. In the present study, the effect of indicaxanthin (Ind), a bioactive pigment from cactus pear fruit, on 7-KC-induced apoptosis of human monocyte/macrophage THP-1 cells was investigated. A pathophysiological condition was simulated by using amounts of 7-KC that can be reached in human atheromatous plaque. Ind was assayed within a micromolar concentration range, consistent with its plasma level after dietary supplementation with cactus pear fruit. Pro-apoptotic effects of 7-KC were assessed by cell cycle arrest, exposure of phosphatidylserine at the plasma membrane, varia…
Mode of cell death induction by pharmacological Vacuolar H+-ATPase (V-ATPase) inhibition.
2012
The vacuolar H+-ATPase (V-ATPase), a multisubunit proton pump, has come into focus as an attractive target in cancer invasion. However, little is known about the role of V-ATPase in cell death, and especially the underlying mechanisms remain mostly unknown. We used the myxobacterial macrolide archazolid B, a potent inhibitor of the V-ATPase, as an experimental drug as well as a chemical tool to decipher V-ATPase-related cell death signaling. We found that archazolid induced apoptosis in highly invasive tumor cells at nanomolar concentrations which was executed by the mitochondrial pathway. Prior to apoptosis induction archazolid led to the activation of a cellular stress response including …