Search results for " apoptosis."
showing 10 items of 359 documents
Age-dependent regulation of antioxidant genes by p38α MAPK in the liver
2018
p38α is a redox sensitive MAPK activated by pro-inflammatory cytokines and environmental, genotoxic and endoplasmic reticulum stresses. The aim of this work was to assess whether p38α controls the antioxidant defense in the liver, and if so, to elucidate the mechanism(s) involved and the age-related changes. For this purpose, we used liver-specific p38α-deficient mice at two different ages: young-mice (4 months-old) and old-mice (24 months-old). The liver of young p38α knock-out mice exhibited a decrease in GSH levels and an increase in GSSG/GSH ratio and malondialdehyde levels. However, old mice deficient in p38α had higher hepatic GSH levels and lower GSSG/GSH ratio than young p38α knock-…
A radiosensitizing effect of artesunate in glioblastoma cells is associated with a diminished expression of the inhibitor of apoptosis protein surviv…
2011
Abstract Background and purpose Novel strategies to overcome an irradiation resistant phenotype may help to increase therapeutic efficacy in glioblastoma multiforme. The present study aimed to elucidate radiation sensitizing properties of artesunate, a semi synthetic derivate of artemisinin and to assess factors involved in this effect. Materials and methods LN229 and U87MG cells were treated with various concentrations of artesunate and radiation response was determined by a colony forming assay. Cell numbers, apoptosis induction, cell cycle distribution, and DNA repair following combined modality treatment were monitored by MTT-, caspase 3/7 assay, cytofluorometry, and γ-H2AX foci formati…
SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells
2012
Abstract SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells to apoptosis induced by TRAIL, a member of TNF-family. In this paper we investigated the effect of SAHA/TRAIL combination in two breast cancer cell lines, the ERα−positive MCF-7 and the ERα−negative MDA-MB231. Treatment of MDA-MB231 and MCF-7 cells with SAHA in combination with TRAIL caused detachment of cells followed by anoikis, a form of apoptosis which occurs after cell detachment, while treatment with SAHA or TRAIL alone did not produce these effects. The effects were more evident in MDA-MB231 cells, which were chosen for ascertaining the mechanism of SAHA/TRAIL action. Our results show…
A novel copper compound, CuNV110, induces apoptosis in tumor cells by dissociation of the Hsp60- pro-caspase 3 complex
2015
The biological activity of CuNV1110, a novel copper chemical compound, has been recently studied on cancer cells and it has been showed that it reduces the cell viability, in a dose and time dependent manner, and induces cell apoptosis. In this study we evaluated the possible mechanisms by which CuNV1110 induces cell apoptosis. In particular we looked at its effects on Hsp60 levels and caspase 3 activation. We used an in vitro model of a pulmonary mucoepidermoid carcinoma (NCI-H292 cells). We found that CuNV1110 reduces the cell viability and induces cell apoptosis in a dose/time dependent manner. Then, we found that Hsp60 levels decrease with the increasing concentrations of CuNV110; by co…
Heat Shock Protein-60 and Risk for Cardiovascular Disease
2011
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. There is growing evidence that molecularchaperones, many of which are heat shock proteins HSPs, are involved in CVD pathogenesis. In this review we focus on HSP60,the human mitochondrial chaperone that also displays extramitochondrial and extracellular functions. HSP60 is typically cytoprotectivebut a number of stress conditions determine its conversion to a potentially toxic molecule for cells and tissues. We present illustrative examplesof specific subtypes of CVD where HSP60 is implicated in the initiation and/or progression of disease. The data not only indicatea pathogenic role for HSP60 but also its …
Red wine extract prevents neuronal apoptosis in vitro and reduces mortality of transgenic mice.
2007
In this work, we have investigated the effects of nutritional antioxidants as antidegenerative agents on glutamate-induced apoptosis in primary cultures of cerebellar granule neurons (CGNs). Glutamate-induced apoptosis is also associated with intracellular [Ca(2+)]i overload, generation of reactive oxygen species (ROS), depression of cell energy metabolism, cytochrome c release, and increase in caspase-3 activity. Pretreatment (3 h) with red wine extract (5 microg/mL) and ascorbic acid (30 microM) blocks glutamate-induced apoptosis in CGNs. In vivo experiments carried out on transgenic mice expressing the human mutated Cu, Zn superoxide dismutase (SOD1) G93A (mSOD1(G93A)) show that mice fed…
Suppressor of cytokine signaling 3 sensitizes anaplastic thyroid cancer to standard chemotherapy
2009
We previously showed that cancer cells from papillary, follicular, and anaplastic thyroid carcinomas produce interleukin-4 and interleukin-10, which counteract the cytotoxic activity of conventional chemotherapy through the up-regulation of antiapoptotic molecules. Here, we identify Janus kinase/signal transducers and activators of transcription (STAT) and phosphatidyl inositol 3-kinase (PI3K)/AKT as the down-stream pathways through which these cytokines confer resistance to cell death in thyroid cancer. We found that the absence of suppressors of cytokine signaling (SOCS) molecules allows the propagation of the survival signaling. Exogenous expression of SOCS1, SOCS3, and SOCS5 in the high…
Parthenolide sensitizes hepatocellular carcinoma cells to trail by inducing the expression of death receptors through inhibition of STAT3 activation
2011
This article shows that HepG2, Hep3B, and SK-Hep1 cells, three lines of human hepatocellular carcinoma (HCC) cells, are resistant to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Parthenolide, a sesquiterpene lactone found in European feverfew, has been shown to exert both anti-inflammatory and anti-cancer activities. This article demonstrates that co-treatment with parthenolide and TRAIL-induced apoptosis with synergistic interactions in the three lines of HCC cells. In order to explain these effects we ascertained that parthenolide increased either at protein or mRNA level the total content of death receptors TRAIL-R1 and -R2 as well as their surfac…
The antitumor activities of curcumin and its isoxazole analogue are not affected by multiple gene expression changes in an MDR model of the MCF-7 bre…
2007
We examined the effects of curcumin and of its isoxazole analogue MR 39 in the MCF-7 breast cancer cell line and in its multidrug-resistant (MDR) variant MCF-7R. In comparison with MCF-7, MCF-7R lacks estrogen receptor alpha (ERalpha) and overexpressess P-glycoprotein (P-gp), different IAPs (inhibitory of apoptosis proteins) and COX-2. Through analyses of the effects on cell proliferation, cycling and death, we have observed that the antitumor activity of curcumin and of the more potent (approximately two-fold) MR 39 is at least equal in the MDR cell line compared to the parental MCF-7. Similar results were observed also in an MDR variant of HL-60 leukemia. RT-PCR evaluations performed in M…