Antioxidants

Our medical research library holds 6 studies published in Antioxidants (2017–2026). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 6 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: MDPI AG
• Published: 2012 to the present, Switzerland
• Language: English
• ISSN: 2076-3921 (electronic)
• Its record in the NLM Catalog

2020s

• Reactive Oxygen Species Drive Cell Migration and PD-L1 Expression via YB-1 Phosphorylation in Pleural Mesothelioma. M. Hashim, G. Timelthaler, D. Kirchhofer, et al. 2026;15(1). PubMed · Publisher · Free full text

  Abstract

  Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X)- and xanthine oxidase (XO)-generated ROS exposure led to increased migration and a more elongated cell shape in mesothelial and PM cells in live-cell videomicroscopy analyses. These effects were associated with the enhanced phosphorylation of ERK, AKT, and YB-1 and the elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time RT-PCR, respectively. The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM.

• A Comprehensive Study of Reactive Oxygen Species Explicit Dosimetry for Pleural Photodynamic Therapy. H. Sun, Y. Ong, M.M. Kim, et al. 2024;13(12). PubMed · Publisher · Free full text

  Abstract

  Photodynamic therapy (PDT) relies on the interactions between light, photosensitizers, and tissue oxygen to produce cytotoxic reactive oxygen species (ROS), primarily singlet oxygen (1O2) through Type II photochemical reactions, along with superoxide anion radicals (O2•-), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH) through Type I mechanisms. Accurate dosimetry, accounting for all three components, is crucial for predicting and optimizing PDT outcomes. Conventional dosimetry tracks only light fluence rate and photosensitizer concentration, neglecting the role of tissue oxygenation. Reactive oxygen species explicit dosimetry (ROSED) quantifies the reacted oxygen species concentration ([ROS]rx) by explicit measurements of light fluence (rate), photosensitizer concentration, and tissue oxygen concentration. Here we determine tissue oxygenation from non-invasive diffuse correlation spectroscopy (DCS) measurement of tumor blood flow using a conversion factor established preclinically. In this study, we have enrolled 24 pleural PDT patients into the study. Of these patients, we are able to obtain data on 20. Explicit dosimetry of light fluence, Photofrin concentration, and tissue oxygenation concentrations were integrated into the ROSED model to calculate [ROS]rx across multiple sites inside the pleural cavity and among different patients. Large inter- and intra-patient heterogeneities in [ROS]rx were observed, despite identical 60 J/cm2 light doses, with mean [ROS]rx,meas of 0.56 ± 0.26 mM for 13 patients with 21 sites, and [ROS]rx,calc1 of 0.48 ± 0.23 mM for 20 patients with 76 sites. This study presented the first comprehensive analysis of clinical ROSED in pleural mesothelioma patients, providing valuable data on future ROSED based pleural PDT that can potentially produce uniform ROS and thus improve the PDT efficacy for Photofrin-mediated pleural PDT.

• Unique Cellular and Biochemical Features of Human Mitochondrial Peroxiredoxin 3 Establish the Molecular Basis for Its Specific Reaction with Thiostrepton. K.J. Nelson, T. Messier, S. Milczarek, et al. 2021;10(2). PubMed · Publisher · Free full text

  Abstract

  A central hallmark of tumorigenesis is metabolic alterations that increase mitochondrial reactive oxygen species (mROS). In response, cancer cells upregulate their antioxidant capacity and redox-responsive signaling pathways. A promising chemotherapeutic approach is to increase ROS to levels incompatible with tumor cell survival. Mitochondrial peroxiredoxin 3 (PRX3) plays a significant role in detoxifying hydrogen peroxide (H2O2). PRX3 is a molecular target of thiostrepton (TS), a natural product and FDA-approved antibiotic. TS inactivates PRX3 by covalently adducting its two catalytic cysteine residues and crosslinking the homodimer. Using cellular models of malignant mesothelioma, we show here that PRX3 expression and mROS levels in cells correlate with sensitivity to TS and that TS reacts selectively with PRX3 relative to other PRX isoforms. Using recombinant PRXs 1-5, we demonstrate that TS preferentially reacts with a reduced thiolate in the PRX3 dimer at mitochondrial pH. We also show that partially oxidized PRX3 fully dissociates to dimers, while partially oxidized PRX1 and PRX2 remain largely decameric. The ability of TS to react with engineered dimers of PRX1 and PRX2 at mitochondrial pH, but inefficiently with wild-type decameric protein at cytoplasmic pH, supports a novel mechanism of action and explains the specificity of TS for PRX3. Thus, the unique structure and propensity of PRX3 to form dimers contribute to its increased sensitivity to TS-mediated inactivation, making PRX3 a promising target for prooxidant cancer therapy.

• Mitochondrial ROS Induce Partial Dedifferentiation of Human Mesothelioma via Upregulation of NANOG. F. Sedlic, F. Seiwerth, A. Sepac, et al. 2020;9(7). PubMed · Publisher · Free full text

  Abstract

  The expression of pluripotency factors is a key regulator of tumor differentiation status and cancer stem cells. The purpose of this study was to examine the expression of pluripotency factors and differentiation status of human mesothelioma and the role of mitochondria in their regulation. We tested the expression of OCT4/POU5F1, NANOG, SOX2, PI3K-AKT pathway and BCL2 genes and proteins in 65 samples of human mesothelioma and 19 samples of normal mesothelium. Mitochondrial membrane potential, reactive oxygen species (ROS) generation and expression of pluripotency factors were also tested in human mesothelioma cell line. Human mesothelium and mesothelioma expressed SOX2, NANOG, PI3K and AKT genes and proteins and POU5F1 gene, whereby NANOG, SOX2 and phosphorylated (activated) AKT were upregulated in mesothelioma. NANOG protein expression was elevated in less differentiated samples of human mesothelioma. The expression of genes of PI3K-AKT pathway correlated with pluripotency factor genes. Mesothelioma cells had functional, but depolarized mitochondria with large capacity to generate ROS. Mitochondrial ROS upregulated NANOG and mitoTEMPO abrogated it. In conclusion, human mesothelioma displays enhanced expression of NANOG, SOX2 and phosphorylated AKT proteins, while elevated NANOG expression correlates with poor differentiation of human mesothelioma. Mitochondria of mesothelioma cells have a large capacity to form ROS and thereby upregulate NANOG, leading to dedifferentiation of mesothelioma.

2010s

• Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605) Reduces Asbestos-Induced Cytotoxicity in an Nrf2-Dependent and -Independent Manner. R.A. Pietrofesa, S. Chatterjee, K. Park, et al. 2018;7(3). PubMed · Publisher · Free full text

  Abstract

  Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2-/-) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm²) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2-/- macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.

• Effects of β-Carotene and Its Cleavage Products in Primary Pneumocyte Type II Cells. C. Haider, F. Ferk, E. Bojaxhi, et al. 2017;6(2). PubMed · Publisher · Free full text

  Abstract

  β-Carotene has been shown to increase the risk of developing lung cancer in smokers and asbestos workers in two large scale trails, the Beta-Carotene and Retinol Efficacy Trial (CARET) and the Alpha-Tocopherol Beta-carotene Cancer Prevention Trial (ATBC). Based on this observation, it was proposed that genotoxic oxidative breakdown products may cause this effect. In support of this assumption, increased levels of sister chromatid exchanges, micronuclei, and chromosomal aberrations were found in primary hepatocyte cultures treated with a mixture of cleavage products (CPs) and the major product apo-8'carotenal. However, because these findings cannot directly be transferred to the lung due to the exceptional biotransformation capacity of the liver, potential genotoxic and cytotoxic effects of β-carotene under oxidative stress and its CPs were investigated in primary pneumocyte type II cells. The results indicate that increased concentrations of β-carotene in the presence of the redox cycling quinone dimethoxynaphthoquinone (DMNQ) exhibit a cytotoxic potential, as evidenced by an increase of apoptotic cells and loss of cell density at concentrations > 10 µM. On the other hand, the analysis of micronucleated cells gave no clear picture due to the cytotoxicity related reduction of mitotic cells. Last, although CPs induced significant levels of DNA strand breaks even at concentrations ≥ 1 µM and 5 µM, respectively, β-carotene in the presence of DMNQ did not cause DNA damage. Instead, β-carotene appeared to act as an antioxidant. These findings are in contrast with what was demonstrated for primary hepatocytes and may reflect different sensitivities to and different metabolism of β-carotene in the two cell types.

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