Search results for "Reactive"
showing 10 items of 1469 documents
Miltirone Induces G2/M Cell Cycle Arrest and Apoptosis in CCRF-CEM Acute Lymphoblastic Leukemia Cells
2015
Miltirone (1) is a diterpene quinone extracted from a well-known Chinese traditional herb (Salvia miltiorrhiza). We investigated the cytotoxic effects of miltirone toward sensitive and multidrug-resistant acute lymphoblastic leukemia cell lines. Miltirone inhibited multidrug-resistant P-glycoprotein (P-gp)-overexpressing CEM/ADR5000 cells better than drug-sensitive CCRF-CEM wild-type cells, a phenomenon termed collateral sensitivity. Flow cytometric analyses revealed that miltirone induced G2/M arrest and apoptosis. Furthermore, miltirone stimulated reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) disruption, which in turn induced DNA damage and activation…
The role of reactive oxygen species and subsequent DNA-damage response in the emergence of resistance towards resveratrol in colon cancer models
2014
AbstractIn spite of the novel strategies to treat colon cancer, mortality rates associated with this disease remain consistently high. Tumour recurrence has been linked to the induction of resistance towards chemotherapy that involves cellular events that enable cancer cells to escape cell death. Treatment of colon cancer mainly implicates direct or indirect DNA-damaging agents and increased repair or tolerances towards subsequent lesions contribute to generate resistant populations. Resveratrol (RSV), a potent chemosensitising polyphenol, might share common properties with chemotherapeutic drugs through its indirect DNA-damaging effects reported in vitro. In this study, we investigated how…
Spectroscopic and DFT Characterization of a Highly Reactive Nonheme FeV–Oxo Intermediate
2018
The reaction of [(PyNMe3)FeII(CF3SO3)2], 1, with excess peracetic acid at −40 °C generates a highly reactive intermediate, 2b(PAA), that has the fastest rate to date for oxidizing cyclohexane by a nonheme iron species. It exhibits an intense 490 nm chromophore associated with an S = 1/2 EPR signal having g-values at 2.07, 2.01, and 1.94. This species was shown to be in a fast equilibrium with a second S = 1/2 species, 2a(PAA), assigned to a low-spin acylperoxoiron(III) center. Unfortunately, contaminants accompanying the 2(PAA) samples prevented determination of the iron oxidation state by Mossbauer spectroscopy. Use of MeO-PyNMe3 (an electron-enriched version of PyNMe3) and cyclohexyl pero…
Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells
2010
BACKGROUND AND PURPOSE Efavirenz (EFV) is widely used in the treatment of HIV-1 infection. Though highly efficient, there is growing concern about EFV-related side effects, the molecular basis of which remains elusive. EXPERIMENTAL APPROACH In vitro studies were performed to address the effect of clinically relevant concentrations of EFV (10, 25 and 50 mu M) on human hepatic cells. KEY RESULTS Cellular proliferation and viability were reduced in a concentration-dependent manner. Analyses of the cell cycle and several cell death parameters (chromatin condensation, phosphatidylserine exteriorization, mitochondrial proapoptotic protein translocation and caspase activation) revealed that EFV tr…
Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.
2013
Respiratory syncytial virus (RSV) causes acute exacerbations in COPD and asthma. RSV infects bronchial epithelial cells (HBE) that trigger RSV associated lung pathology. This study explores whether the phosphodiesterase 4 (PDE4) inhibitor Roflumilast N-oxide (RNO), alters RSV infection of well-differentiated HBE (WD-HBE) in vitro. WD-HBE were RSV infected in the presence or absence of RNO (0.1-100 nM). Viral infection (staining of F and G proteins, nucleoprotein RNA level), mRNA of ICAM-1, ciliated cell markers (digital high speed videomicroscopy, β-tubulin immunofluorescence, Foxj1 and Dnai2 mRNA), Goblet cells (PAS), mRNA of MUC5AC and CLCA1, mRNA and protein level of IL-13, IL-6, IL-8, T…
Dynamic changes in the subcellular distribution of the tobacco ROS-producing enzyme RBOHD in response to the oomycete elicitor cryptogein.
2014
Highlight text The oomycete elicitor cryptogein triggers the relocation of RBOHD from intracellular compartments to the plasma membrane in tobacco cells. This suggests that intracellular trafficking is a potential determinant of RBOHD activity.
A loop involving NRF2, miR‐29b‐1‐5p and AKT, regulates cell fate of MDA‐MB‐231 triple‐negative breast cancer cells
2019
The present study shows that nuclear factor erythroid 2-related factor 2 (NRF2) and miR-29b-1-5p are two opposite forces which could regulate the fate of MDA-MB-231 cells, the most studied triple-negative breast cancer (TNBC) cell line. We show that NRF2 activation stimulates cell growth and markedly reduces reactive oxygen species (ROS) generation, whereas miR-29b-1-5p overexpression increases ROS generation and reduces cell proliferation. Moreover, NRF2 downregulates miR-29b-1-5p expression, whereas miR-29b-1-5p overexpression decreases p-AKT and p-NRF2. Furthermore, miR-29b-1-5p overexpression induces both inhibition of DNA N-methyltransferases (DNMT1, DNMT3A, and DNMT3B) expression and …
Oxidative stress impairs the repair of oxidative DNA base modifications in human skin fibroblasts and melanoma cells.
2008
Irradiation of mammalian cells with solar light is associated with the generation of reactive oxygen species (ROS) and oxidative stress, which is mediated in part by endogenous photosensitizers absorbing in the visible range of the solar spectrum. Accordingly, oxidative DNA base modifications such as 7,8-dihydro-8-oxoguanine (8-oxoG) are the predominant types of DNA damage in cells irradiated at wavelengths >400 nm. We have analysed the repair of oxidative purine modifications in human skin fibroblasts and melanoma cells using an alkaline elution technique, both under normal conditions and after depletion of glutathione. Similar repair rates were observed in fibroblasts and melanoma cells f…
UVA irradiation induces relocalisation of the DNA repair protein hOGG1 to nuclear speckles
2006
The DNA glycosylase hOGG1 initiates base excision repair (BER) of oxidised purines in cellular DNA. Using confocal microscopy and biochemical cell fractionation experiments we show that, upon UVA irradiation of human cells, hOGG1 is recruited from a soluble nucleoplasmic localisation to the nuclear matrix. More specifically, after irradiation, hOGG1 forms foci colocalising with the nuclear speckles, organelles that are interspersed between chromatin domains and that have been associated with transcription and RNA-splicing processes. The use of mutant forms of hOGG1 unable to bind the substrate showed that relocalisation of hOGG1 does not depend on the recognition of the DNA lesion by the en…
Role of Endogenous Oxidative DNA Damage in Carcinogenesis: What Can We Learn from Repair-Deficient Mice?
2002
Basal steady-state levels of oxidative DNA base modifications such as 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG) are observed in all types of cells, most probably due to a continuous generation of reactive oxygen species (ROS) in the cellular oxygen metabolism, and it has long been suspected that they might play an important role in the initiation of carcinogenesis. Experimental evidence for this assumption can be obtained by studying the effects of a modulation of the steady-state levels, either by in- or decreasing the generation of oxidative DNA damage, on spontaneous mutation rates and cancer incidence. However, clear answers have not yet been obtained by these strategies. It is still…