scholarly journals Oxidative Stress in Cancer Cell Metabolism

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 642
Author(s):  
Saniya Arfin ◽  
Niraj Kumar Jha ◽  
Saurabh Kumar Jha ◽  
Kavindra Kumar Kesari ◽  
Janne Ruokolainen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Cell Metabolism ◽  
Redox Balance ◽  
Cancer Therapies ◽  
Ros Production ◽  
Tumor Cell Death ◽  
Antioxidant Defense Systems ◽  
Diseased State

Reactive oxygen species (ROS) are important in regulating normal cellular processes whereas deregulated ROS leads to the development of a diseased state in humans including cancers. Several studies have been found to be marked with increased ROS production which activates pro-tumorigenic signaling, enhances cell survival and proliferation and drives DNA damage and genetic instability. However, higher ROS levels have been found to promote anti-tumorigenic signaling by initiating oxidative stress-induced tumor cell death. Tumor cells develop a mechanism where they adjust to the high ROS by expressing elevated levels of antioxidant proteins to detoxify them while maintaining pro-tumorigenic signaling and resistance to apoptosis. Therefore, ROS manipulation can be a potential target for cancer therapies as cancer cells present an altered redox balance in comparison to their normal counterparts. In this review, we aim to provide an overview of the generation and sources of ROS within tumor cells, ROS-associated signaling pathways, their regulation by antioxidant defense systems, as well as the effect of elevated ROS production in tumor progression. It will provide an insight into how pro- and anti-tumorigenic ROS signaling pathways could be manipulated during the treatment of cancer.

scholarly journals Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 19
Author(s):  
Lidia de Bari ◽  
Andrea Scirè ◽  
Cristina Minnelli ◽  
Laura Cianfruglia ◽  
Miklos Peter Kalapos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Function ◽  
Cell Metabolism ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Dependent Manner ◽  
Ros Production ◽  
Glyoxalase Ii ◽  
Cytotoxic Compound ◽  
Oxidative Damages

Reactive oxygen species (ROS) are produced constantly inside the cells as a consequence of nutrient catabolism. The balance between ROS production and elimination allows to maintain cell redox homeostasis and biological functions, avoiding the occurrence of oxidative distress causing irreversible oxidative damages. A fundamental player in this fine balance is reduced glutathione (GSH), required for the scavenging of ROS as well as of the reactive 2-oxoaldehydes methylglyoxal (MGO). MGO is a cytotoxic compound formed constitutively as byproduct of nutrient catabolism, and in particular of glycolysis, detoxified in a GSH-dependent manner by the glyoxalase pathway consisting in glyoxalase I and glyoxalase II reactions. A physiological increase in ROS production (oxidative eustress, OxeS) is promptly signaled by the decrease of cellular GSH/GSSG ratio which can induce the reversible S-glutathionylation of key proteins aimed at restoring the redox balance. An increase in MGO level also occurs under oxidative stress (OxS) conditions probably due to several events among which the decrease in GSH level and/or the bottleneck of glycolysis caused by the reversible S-glutathionylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase. In the present review, it is shown how MGO can play a role as a stress signaling molecule in response to OxeS, contributing to the coordination of cell metabolism with gene expression by the glycation of specific proteins. Moreover, it is highlighted how the products of MGO metabolism, S-D-lactoylglutathione (SLG) and D-lactate, which can be taken up and metabolized by mitochondria, could play important roles in cell response to OxS, contributing to cytosol-mitochondria crosstalk, cytosolic and mitochondrial GSH pools, energy production, and the restoration of the GSH/GSSG ratio. The role for SLG and glyoxalase II in the regulation of protein function through S-glutathionylation under OxS conditions is also discussed. Overall, the data reported here stress the need for further studies aimed at understanding what role the evolutionary-conserved MGO formation and metabolism can play in cell signaling and response to OxS conditions, the aberration of which may importantly contribute to the pathogenesis of diseases associated to elevated OxS.

scholarly journals Effect of Redox Balance Alterations on Cellular Localization of LAT and Downstream T-Cell Receptor Signaling Pathways

2002 ◽  
Vol 22 (2) ◽  
pp. 400-411 ◽  
Author(s):  
Sonja I. Gringhuis ◽  
Ellen A. M. Papendrecht-van der Voort ◽  
Angela Leow ◽  
E. W. Nivine Levarht ◽  
Ferdinand C. Breedveld ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
T Lymphocytes ◽  
Signaling Pathways ◽  
T Cell Receptor ◽  
Cellular Localization ◽  
Redox Balance ◽  
Cell Receptor ◽  
Chronic Oxidative Stress ◽  
Membrane Displacement

ABSTRACT The integral membrane protein linker for activation of T cells (LAT) is a central adapter protein in the T-cell receptor (TCR)-mediated signaling pathways. The cellular localization of LAT is extremely sensitive to intracellular redox balance alterations. Reduced intracellular levels of the antioxidant glutathione (GSH), a hallmark of chronic oxidative stress, resulted in the membrane displacement of LAT, abrogated TCR-mediated signaling and consequently hyporesponsiveness of T lymphocytes. The membrane displacement of LAT is accompanied by a considerable difference in the mobility of LAT upon native and nonreducing denaturing polyacrylamide gel electrophoresis analysis, a finding indicative of a conformational change. Targeted mutation of redox-sensitive cysteine residues within LAT created LAT mutants which remain membrane anchored under conditions of chronic oxidative stress. The expression of redox-insensitive LAT mutants allows for restoration of TCR-mediated signal transduction, whereas CD28-mediated signaling pathways remained impaired. These results are indicative that the membrane displacement of LAT as a result of redox balance alterations is a consequence of a conformational change interfering with the insertion of LAT into the plasma membrane. Conclusively, the data suggest a role for LAT as a crucial intermediate in the sensitivity of TCR signaling and hence T lymphocytes toward chronic oxidative stress.

scholarly journals L-Carnitine: An Antioxidant Remedy for the Survival of Cardiomyocytes under Hyperglycemic Condition

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Fernanda Vacante ◽  
Pamela Senesi ◽  
Anna Montesano ◽  
Alice Frigerio ◽  
Livio Luzi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathways ◽  
Stress Condition ◽  
Cardiac Cells ◽  
Ros Production ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Rat Cardiomyocytes ◽  
Oxidative Stress Condition

Background. Metabolic alterations as hyperglycemia and inflammation induce myocardial molecular events enhancing oxidative stress and mitochondrial dysfunction. Those alterations are responsible for a progressive loss of cardiomyocytes, cardiac stem cells, and consequent cardiovascular complications. Currently, there are no effective pharmacological measures to protect the heart from these metabolic modifications, and the development of new therapeutic approaches, focused on improvement of the oxidative stress condition, is pivotal. The protective effects of levocarnitine (LC) in patients with ischemic heart disease are related to the attenuation of oxidative stress, but LC mechanisms have yet to be fully understood. Objective. The aim of this work was to investigate LC’s role in oxidative stress condition, on ROS production and mitochondrial detoxifying function in H9c2 rat cardiomyocytes during hyperglycemia. Methods. H9c2 cells in the hyperglycemic state (25 mmol/L glucose) were exposed to 0.5 or 5 mM LC for 48 and 72 h: LC effects on signaling pathways involved in oxidative stress condition were studied by Western blot and immunofluorescence analysis. To evaluate ROS production, H9c2 cells were exposed to H2O2 after LC pretreatment. Results. Our in vitro study indicates how LC supplementation might protect cardiomyocytes from oxidative stress-related damage, preventing ROS formation and activating antioxidant signaling pathways in hyperglycemic conditions. In particular, LC promotes STAT3 activation and significantly increases the expression of antioxidant protein SOD2. Hyperglycemic cardiac cells are characterized by impairment in mitochondrial dysfunction and the CaMKII signal: LC promotes CaMKII expression and activation and enhancement of AMPK protein synthesis. Our results suggest that LC might ameliorate metabolic aspects of hyperglycemic cardiac cells. Finally, LC doses herein used did not modify H9c2 growth rate and viability. Conclusions. Our novel study demonstrates that LC improves the microenvironment damaged by oxidative stress (induced by hyperglycemia), thus proposing this nutraceutical compound as an adjuvant in diabetic cardiac regenerative medicine.

scholarly journals ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Anastasiya V. Snezhkina ◽  
Anna V. Kudryavtseva ◽  
Olga L. Kardymon ◽  
Maria V. Savvateeva ◽  
Nataliya V. Melnikova ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Genome Instability ◽  
Cell Metabolism ◽  
Cell Activity ◽  
Current Data ◽  
Antioxidant Systems ◽  
Ros Generation ◽  
Tumor Cell Death ◽  
Antioxidant Defense Systems ◽  
Cellular Compartments

Reactive oxygen species (ROS) are by-products of normal cell activity. They are produced in many cellular compartments and play a major role in signaling pathways. Overproduction of ROS is associated with the development of various human diseases (including cancer, cardiovascular, neurodegenerative, and metabolic disorders), inflammation, and aging. Tumors continuously generate ROS at increased levels that have a dual role in their development. Oxidative stress can promote tumor initiation, progression, and resistance to therapy through DNA damage, leading to the accumulation of mutations and genome instability, as well as reprogramming cell metabolism and signaling. On the contrary, elevated ROS levels can induce tumor cell death. This review covers the current data on the mechanisms of ROS generation and existing antioxidant systems balancing the redox state in mammalian cells that can also be related to tumors.

scholarly journals Transforming Growth Factor-β and Oxidative Stress in Cancer: A Crosstalk in Driving Tumor Transformation

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3093
Author(s):  
Valeria Ramundo ◽  
Giuliana Giribaldi ◽  
Elisabetta Aldieri
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Cancer Cell ◽  
Transforming Growth Factor ◽  
Cell Metabolism ◽  
Transforming Growth Factor Β ◽  
Ros Production ◽  
Redox Imbalance ◽  
Cancer Cell Metabolism ◽  
And Oxidative Stress

Cancer metabolism involves different changes at a cellular level, and altered metabolic pathways have been demonstrated to be heavily involved in tumorigenesis and invasiveness. A crucial role for oxidative stress in cancer initiation and progression has been demonstrated; redox imbalance, due to aberrant reactive oxygen species (ROS) production or deregulated efficacy of antioxidant systems (superoxide dismutase, catalase, GSH), contributes to tumor initiation and progression of several types of cancer. ROS may modulate cancer cell metabolism by acting as secondary messengers in the signaling pathways (NF-kB, HIF-1α) involved in cellular proliferation and metastasis. It is known that ROS mediate many of the effects of transforming growth factor β (TGF-β), a key cytokine central in tumorigenesis and cancer progression, which in turn can modulate ROS production and the related antioxidant system activity. Thus, ROS synergize with TGF-β in cancer cell metabolism by increasing the redox imbalance in cancer cells and by inducing the epithelial mesenchymal transition (EMT), a crucial event associated with tumor invasiveness and metastases. Taken as a whole, this review is addressed to better understanding this crosstalk between TGF-β and oxidative stress in cancer cell metabolism, in the attempt to improve the pharmacological and therapeutic approach against cancer.

scholarly journals Effect of tirapazamine on selected kidney parameters in rats treated with cisplatin

2019 ◽  
Vol 32 (1) ◽  
pp. 18-22
Author(s):  
Marcin Sysa ◽  
Kamil Pawlowski ◽  
Piotr Slabczynski ◽  
Franciszek Burdan ◽  
Jaroslaw Dudka
Keyword(s):  
Oxidative Stress ◽  
Adverse Effect ◽  
Protein Concentration ◽  
Cell Metabolism ◽  
Redox Balance ◽  
Cytotoxic Agents ◽  
Cytostatic Drugs ◽  
Redox Equilibrium ◽  
Oxidative Stress Parameters ◽  
Stress Parameters

Abstract Hypoxic cancer cells are more aggressive and responsible for more efficient metastasis and recurrence. It seems worth-while, hence, to supplement current cytostatic drugs therapy (i.e. cisplatin) with hypoxia cytotoxic agents (i.e. tirapazamine), the toxicity of which is activated by hypoxia. Cisplatin and tirapazamine can change a redox equilibrium and consequently lead to changes in cell metabolism, fibrosis and apoptosis. The aim of this study was to evaluate the cisplatin/tirapazamine toxicological synergism. In doing so we tested selected kidney oxidative stress parameters, as well as nephrotoxicity markers, in plasma and urine. Once a week for 6 weeks, rats received intraperitoneally two doses of tirapazamine (5 or 10 mg/kg bw), 2 hours before cisplatin (2 mg/kg bw) was applied. Our results show that Tirapazamine (TP) had no significant adverse effect on the redox balance, oxidative stress and kidney function in rats receiving cisplatin (CP). However, TP significantly increased protein concentration in the kidneys of rats. In all tested groups, a significant decrease in NADH concentration in kidneys was recorded, which could indicate disorder in the cell metabolism. TP also was found to have prevented bacterial infection caused by CP. In summary, there was no nephrotoxic synergy of TP with CP at an unacceptable level.

scholarly journals The Effect of Selected Dental Materials Used in Conservative Dentistry, Endodontics, Surgery, and Orthodontics as Well as during the Periodontal Treatment on the Redox Balance in the Oral Cavity

2020 ◽  
Vol 21 (24) ◽  
pp. 9684
Author(s):  
Izabela Zieniewska ◽  
Mateusz Maciejczyk ◽  
Anna Zalewska
Keyword(s):  
Oxidative Stress ◽  
Oral Cavity ◽  
Dental Treatment ◽  
Cell Metabolism ◽  
Redox Homeostasis ◽  
Dental Materials ◽  
Redox Balance ◽  
Titanium Implants ◽  
Dental Composite ◽  
Root Canal Filling

Oxidative stress (OS) is a redox homeostasis disorder that results in oxidation of cell components and thus disturbs cell metabolism. OS is induced by numerous internal as well as external factors. According to recent studies, dental treatment may also be one of them. The aim of our work was to assess the effect of dental treatment on the redox balance of the oral cavity. We reviewed literature available in PubMed, Medline, and Scopus databases, including the results from 2010 to 2020. Publications were searched according to the keywords: oxidative stress and dental monomers; oxidative stress and amalgam; oxidative stress and periodontitis, oxidative stress and braces, oxidative stress and titanium; oxidative stress and dental implants, oxidative stress and endodontics treatment, oxidative stress and dental treatment; and oxidative stress and dental composite. It was found that dental treatment with the use of composites, amalgams, glass-ionomers, materials for root canal filling/rinsing, orthodontic braces (made of various metal alloys), titanium implants, or whitening agents can disturb oral redox homeostasis by affecting the antioxidant barrier and increasing oxidative damage to salivary proteins, lipids, and DNA. Abnormal saliva secretion/composition was also observed in dental patients in the course of OS. It is suggested that the addition of antioxidants to dental materials or antioxidant therapy applied during dental treatment could protect the patient against harmful effects of OS in the oral cavity.

scholarly journals Oxidative Stress Induced by the Deubiquitinase Inhibitor b-AP15 Is Associated with Mitochondrial Impairment

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaonan Zhang ◽  
Belén Espinosa ◽  
Amir Ata Saei ◽  
Padraig D'Arcy ◽  
Roman A. Zubarev ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tumor Cells ◽  
Acquired Resistance ◽  
Cancer Therapies ◽  
Oxygen Species ◽  
Apoptosis Induction ◽  
Proteotoxic Stress ◽  
Dub Inhibitor ◽  
Mitochondrial Origin ◽  
In Cells

Inhibitors of the 20S proteasome such as bortezomib are cytotoxic to tumor cells and have been proven to be valuable for the clinical management of multiple myeloma. The therapeutic efficacy of bortezomib is, however, hampered by the emergence of acquired resistance. Available data suggest that blocking proteasome activity at the level of proteasome-associated deubiquitinases (DUBs) provides a mechanism to overcome resistance to bortezomib and also to other cancer therapies. The small molecule b-AP15 is an inhibitor of proteasome-associated DUB activity that induces both proteotoxic stress and increases in the levels of reactive oxygen species (ROS) in tumor cells. Antioxidants have been shown to decrease apoptosis induction by b-AP15 and we here addressed the question of the mechanism of redox perturbation by this compound. We show that oxidative stress induction by b-AP15 is abrogated in cells deprived of mitochondrial DNA (ρ0cells). We also show associations between the level of proteotoxic stress, the degree of mitochondrial dysfunction, and the extent of induction of hemeoxygenase-1 (HO-1), a target of the redox-regulated Nrf-2 transcription factor. Decreased expression of COX5b (cytochrome c oxidase subunit 5b) and TOMM34 (translocase of outer mitochondrial membrane 34) was observed in b-AP15-treated cells. These findings suggest a mitochondrial origin of the increased levels of ROS observed in cells exposed to the DUB inhibitor b-AP15.

scholarly journals Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1090
Author(s):  
Komsak Pintha ◽  
Wittaya Chaiwangyen ◽  
Supachai Yodkeeree ◽  
Maitree Suttajit ◽  
Payungsak Tantipaiboonwong
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Rosmarinic Acid ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
A549 Cells ◽  
Akt Signaling ◽  
Seed Meal ◽  
Ros Production ◽  
Perilla Seed

Particulate matter from forest fires (PMFF) is an environmental pollutant causing oxidative stress, inflammation, and cancer cell metastasis due to the presence of polycyclic aromatic hydrocarbons (PAHs). Perilla seed meal contains high levels of polyphenols, including rosmarinic acid (RA). The aim of this study is to determine the anti-oxidative stress, anti-inflammation, and anti-metastasis actions of rosmarinic acid rich fraction (RA-RF) from perilla seed meal and its underlying molecular mechanisms in A549 cells exposed to PMFF. PMFF samples were collected via the air sampler at the University of Phayao, Thailand, and their PAH content were analyzed using GC-MS. Fifteen PAH compounds were detected in PMFF. The PMFF significantly induced intracellular reactive oxygen species (ROS) production, the mRNA expression of pro-inflammatory cytokines, MMP-9 activity, invasion, migration, the overexpression of c-Jun and p-65-NF-κB, and Akt phosphorylation. Additionally, the RA-RF significantly reduced ROS production, IL-6, IL-8, TNF-α, and COX-2. RA-RF could also suppress MMP-9 activity, migration, invasion, and the phosphorylation activity of c-Jun, p-65-NF-κB, and Akt. Our findings revealed that RA-RF has antioxidant, anti-inflammatory, and anti-metastasis properties via c-Jun, p-65-NF-κB, and Akt signaling pathways. RA-RF may be further developed as an inhalation agent for the prevention of lung inflammation and cancer metastasis induced by PM exposure.

Ambidextrous Approach To Disrupt Redox Balance in Tumor Cells with Increased ROS Production and Decreased GSH Synthesis for Cancer Therapy

2019 ◽  
Vol 11 (30) ◽  
pp. 26722-26730 ◽  
Author(s):  
Longfa Kou ◽  
Rui Sun ◽  
Shuyi Xiao ◽  
Yawen Zheng ◽  
Zhiwei Chen ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Tumor Cells ◽  
Redox Balance ◽  
Ros Production
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