Search results for "toxicity"

Triclosan-Evoked Neurotoxicity Involves NMDAR Subunits with the Specific Role of GluN2A in Caspase-3-Dependent Apoptosis

2018

Triclosan (TCS) is an antimicrobial agent that is used extensively in personal care and in sanitising products. A number of studies have shown the presence of TCS in different human tissues such as blood, adipose tissue, the liver, brain as well as in breast milk and urine. N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are widely expressed in the central nervous system and which play key roles in excitatory synaptic transmission. There is, however, no data on the involvement of NMDAR subunits in the apoptotic and neurotoxic effects of TCS. Our experiments are the first to show that TCS used at environmentally relevant concentrations evoked NMDA-dependent effe…

The anti-cancer drug doxorubicin induces substantial epigenetic changes in cultured cardiomyocytes.

2019

Abstract The anthracycline doxorubicin (DOX) is widely used in cancer therapy with the limitation of cardiotoxicity leading to the development of congestive heart failure. DOX-induced oxidative stress and changes of the phosphoproteome as well as epigenome were described but the exact mechanisms of the adverse long-term effects are still elusive. Here, we tested the impact of DOX treatment on cell death, oxidative stress parameters and expression profiles of proteins involved in epigenetic pathways in a cardiomyocyte cell culture model. Markers of oxidative stress, apoptosis and expression of proteins involved in epigenetic processes were assessed by immunoblotting in cultured rat myoblasts…

The alkaloid, soyauxinium chloride, displays remarkable cytotoxic effects towards a panel of cancer cells, inducing apoptosis, ferroptosis and necrop…

2020

Abstract The cytotoxic potential of a naturally occurring indoloquinazoline alkaloid, soyauxinium chloride (SCHL), was determined on a broad panel of animal and human cancer cell lines, including various sensitive and drug-resistant phenotypes. The cytotoxicity, SCHL-induced autophagic, ferroptotic, and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). Caspase-Glo assay was used to detect the activity of caspases using spectrophotometric analysis. Flow cytometry was applied for cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). SCHL and doxorubicin (ref…

Cytotoxicity of a naturally occuring spirostanol saponin, progenin III, towards a broad range of cancer cell lines by induction of apoptosis, autopha…

2020

Abstract This study was aimed to investigate the cytotoxic potential of a natural compound, progenin III on a broad range of cancer cell lines, including various sensitive and drug-resistant phenotypes. The cytotoxicity, progenin III-induced autophagic, ferroptotic and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). Spectrophotometric analysis of caspases activity was performed using caspase-Glo assay. Flow cytometry was applied for cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). Progenin III and the reference molecule, doxorubicin exerted cytotoxi…

Alternariol induce toxicity via cell death and mitochondrial damage on Caco-2 cells

2015

Alternariol (AOH), a mycotoxin produced by Alternaria sp, appears as food contaminant in fruit, vegetables and cereal products. Its toxicity has been demonstrated, but the mechanisms involved have not been elucidated yet. In this study, the pathways triggered by AOH and degradation products generated on Caco-2 cells were evaluated. Cells were exposed to AOH sub-cytotoxic concentrations of 15, 30 and 60 μM. Cell cycle disruption, the induction of apoptosis/necrosis and changes in mitochondrial membrane potential (Δψm) after 24 and 48 h was asses by flow cytometry. Also, AOH and its degradation products were evaluated after 24 and 48 h by high-performance liquid chromatography with tandem mas…

Cytotoxicity of epunctanone and four other phytochemicals isolated from the medicinal plants Garcinia epunctata and Ptycholobium contortum towards mu…

2018

Abstract Introduction Resistance of cancer cells is a serious impediment to chemotherapy and several phytochemicals are active against multi-drug resistant (MDR) phenotypes. The cytotoxicity of five naturally occurring compounds: betulin (1), mundulea lactone (2), seputhecarpan A (3), seputheisoflavone (4) and epunctanone (5) was evaluated on a panel of 9 cancer cell lines including various sensitive and drug-resistant cell lines. The modes of action of compound 5 were further investigated. Methods The resazurin reduction assay was used to evaluate cytotoxicity of samples and ferroptotic cell death induced by compound 5; caspase-Glo assay was used to detect the activation of caspases in CCR…

Protective function of autophagy during VLCFA-induced cytotoxicity in a neurodegenerative cell model

2019

Abstract In recent years, a particular interest has focused on the accumulation of fatty acids with very long chains (VLCFA) in the occurrence of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis or dementia. Indeed, it seems increasingly clear that this accumulation of VLCFA in the central nervous system is accompanied by a progressive demyelination resulting in death of neuronal cells. Nevertheless, molecular mechanisms by which VLCFA result in toxicity remain unclear. This study highlights for the first time in 3 different cellular models (oligodendrocytes 158 N, primary mouse brain culture, and patient fibroblasts) the types of cell death involved where VLCFA-in…

Leaf and Root Extracts from Campomanesia adamantium (Myrtaceae) Promote Apoptotic Death of Leukemic Cells via Activation of Intracellular Calcium and…

2017

Phytochemical studies are seeking new alternatives to prevent or treat cancer, including different types of leukemias. Campomanesia adamantium, commonly known as guavira or guabiroba, exhibits pharmacological properties including antioxidant, antimicrobial, and antiproliferative activities. Considering the anticancer potential of this plant species, the aim of this study was to evaluate the antileukemic activity and the chemical composition of aqueous extracts from the leaves (AECL) and roots (AECR) of C. adamantium and their possible mechanisms of action. The extracts were analyzed by LC-DAD-MS, and their constituents were identified based on the UV, MS, and MS/MS data. The AECL and AECR s…

2018

High grade gliomas are the most common brain tumors in adult. These tumors are characterized by a high infiltration in microglial cells and macrophages. The immunosuppressive tumor environment is known to orient immune cells toward a pro-tumoral and anti-inflammatory phenotype. Therefore, the current challenge for cancer therapy is to find a way to reorient macrophages toward an antitumoral phenotype. Previously, we demonstrated that macrophages secreted antitumoral factors when they were invalidated for the proprotein converstase 1/3 (PC1/3) and treated with LPS. However, achieving an activation of macrophages via LPS/TLR4/Myd88-dependent pathway appears yet unfeasible in cancer patients. …

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…