Search results for " SURVIVAL"
showing 10 items of 1946 documents
Mechanisms of beauvericin toxicity and antioxidant cellular defense
2015
Beauvericin (BEA) is a secondary metabolite produced by many species of fungus Fusarium. This study determines the injury (cell viability, cell proliferation, mitochondrial membrane potential, cell death and DNA damage) and the intracellular defense mechanisms (catalase and superoxide dismutase) in Chinese Hamster ovary (CHO-K1) cells after BEA exposure. The results obtained in this study demonstrated that BEA induces cytotoxicity in a dose- and time-dependent manner in CHO-K1 cells. Moreover, disruption in mitochondrial enzymatic activity and cell proliferation has been observed after BEA exposure, which can lead or be consequence of cell death. BEA inhibits cell proliferation by arresting…
BAX inhibitor-1 is a Ca(2+) channel critically important for immune cell function and survival.
2015
The endoplasmic reticulum (ER) serves as the major intracellular Ca(2+) store and has a role in the synthesis and folding of proteins. BAX (BCL2-associated X protein) inhibitor-1 (BI-1) is a Ca(2+) leak channel also implicated in the response against protein misfolding, thereby connecting the Ca(2+) store and protein-folding functions of the ER. We found that BI-1-deficient mice suffer from leukopenia and erythrocytosis, have an increased number of splenic marginal zone B cells and higher abundance and nuclear translocation of NF-κB (nuclear factor-κ light-chain enhancer of activated B cells) proteins, correlating with increased cytosolic and ER Ca(2+) levels. When put into culture, purifie…
Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mous…
2020
In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to have health benefits, to inhibit the cytotoxic effects of very long-chain fatty acids (C24:0, C26:0), which can contribute to the development of some neurodegenerative diseases. The effect of DHA (50 µ
Peroxisome proliferator-activated receptor-γ coactivator-1α mediates neuroprotection against excitotoxic brain injury in transgenic mice: role of mit…
2016
Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator involved in the regulation of mitochondrial biogenesis and cell defense. The functions of PGC-1α in physiology of brain mitochondria are, however, not fully understood. To address this we have studied wild-type and transgenic mice with a two-fold overexpression of PGC-1α in brain neurons. Data showed that the relative number and basal respiration of brain mitochondria were increased in PGC-1α transgenic mice compared with wild-type mitochondria. These changes occurred concomitantly with altered levels of proteins involved in oxidative phosphorylation (OXPHOS) as studied by proteomi…
Biological activity of PtIV prodrugs triggered by riboflavin-mediated bioorthogonal photocatalysis
2018
AbstractWe have recently demonstrated that riboflavin (Rf) functions as unconventional bioorthogonal photocatalyst for the activation of PtIV prodrugs. In this study, we show how the combination of light and Rf with two PtIV prodrugs is a feasible strategy for light-mediated pancreatic cancer cell death induction. In Capan-1 cells, which have high tolerance against photodynamic therapy, Rf-mediated activation of the cisplatin and carboplatin prodrugs cis,cis,trans-[Pt(NH3)2(Cl)2(O2CCH2CH2CO2H)2] (1) and cis,cis,trans-[Pt(NH3)2(CBDCA)(O2CCH2CH2CO2H)2] (2, where CBDCA = cyclobutane dicarboxylate) resulted in pronounced reduction of the cell viability, including under hypoxia conditions. Such …
Kinase-independent functions of RIPK1 regulate hepatocyte survival and liver carcinogenesis.
2017
The mechanisms that regulate cell death and inflammation play an important role in liver disease and cancer. Receptor-interacting protein kinase 1 (RIPK1) induces apoptosis and necroptosis via kinase-dependent mechanisms and exhibits kinase-independent prosurvival and proinflammatory functions. Here, we have used genetic mouse models to study the role of RIPK1 in liver homeostasis, injury, and cancer. While ablating either RIPK1 or RelA in liver parenchymal cells (LPCs) did not cause spontaneous liver pathology, mice with combined deficiency of RIPK1 and RelA in LPCs showed increased hepatocyte apoptosis and developed spontaneous chronic liver disease and cancer that were independent of TNF…
SERCA and P-glycoprotein inhibition and ATP depletion are necessary for celastrol-induced autophagic cell death and collateral sensitivity in multidr…
2019
Multidrug resistance (MDR) represents an obstacle in anti-cancer therapy. MDR is caused by multiple mechanisms, involving ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp), which reduces intracellular drug levels to sub-therapeutic concentrations. Therefore, sensitizing agents retaining effectiveness against apoptosis- or drug-resistant cancers are desired for the treatment of MDR cancers. The sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump is an emerging target to overcome MDR, because of its continuous expression and because the calcium transport function is crucial to the survival of tumor cells. Previous studies showed that SERCA inhibitors exhibit anti-c…
Aβ Induces Excitotoxicity Mediated by APC/C-Cdh1 Depletion That Can Be Prevented by Glutaminase Inhibition Promoting Neuronal Survival
2016
AbstractThe E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated by the fizzy-related protein homolog/CDC20-like protein 1 (cdh1) in post-mitotic neurons. Growing evidence suggests that dysregulation of APC/C-Cdh1 is involved in neurodegenerative diseases. Here we show in neurons that oligomers of amyloid beta (Aβ), a peptide related to Alzheimer’s disease, cause proteasome-dependent degradation of cdh1. This leads to a subsequent increase in glutaminase (a degradation target of APC/C-Cdh1), which causes an elevation of glutamate levels and further intraneuronal Ca2+ dysregulation, resulting in neuronal apoptosis. Glutaminase inhibition prevents glutamate excitotoxi…
Oral vinorelbine versus etoposide with cisplatin and chemo-radiation as treatment in patients with stage III non-small cell lung cancer: A randomized…
2019
Objectives: Concomitant chemo-radiation is the standard treatment for unresectable stage III non-small cell lung cancer (LA-NSCLC), The aim of this study was to assess the safety and efficacy of oral vinorelbine and cisplatin (OVP) compared with etoposide and cisplatin (EP), both in combination with radiotherapy, in this setting. Material and methods: An open-label, randomized phase II trial was undertaken including 23 hospitals in Spain. Adults with untreated unresectable stage III NSCLC were randomizedl:1 to receive: oral vinorelbine (days 1 and 8 with cisplatin on day 1 in 3-week cycles; 2 cycles of induction, 2 cycles in concomitance) or etoposide (days 1-5 and 29-32 with cisplatin on d…
Cytotoxic activity of the histone deacetylase 3-Selective inhibitor Pojamide on MDA-MB-231 triple-negative breast cancer cells
2019
We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide (N1-(2-aminophenyl)-N8-ferrocenyloctanediamide) and its two derivatives N1-(2-aminophenyl)-N6-ferrocenyladipamide and N1-(2-aminophenyl)-N8-ferroceniumoctanediamide tetrafluoroborate on triple-negative MDA-MB-231 breast cancer cells. Viability/growth assays indicated that only the first two compounds at 70 &mu