Redox Homeostasis in Cancers

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (20 January 2024) | Viewed by 2548

Special Issue Editor

Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
Interests: redox biology; biochemistry; molecular biology; cancer biology and immunology; drug

Special Issue Information

Dear Colleagues,

Reactive oxygen species (ROS) can oxidize cysteine residues and functionally influence a variety of proteins through alterations at their active centers. Therefore, redox homeostasis is a major regulator of physiological and pathological events. In cancer cells, appropriate levels of intracellular ROS are essential for signal transduction. Excessive accumulation or depletion of ROS can influence signaling pathways, sometimes resulting in cell death, suggesting that this may be a viable approach to the inhibition of cancer progression with either pro-oxidant or antioxidant therapies. Cancer cells experience higher oxidative stress because of the hyperactivation of anabolic pathways, increased mitochondrial function, malfunction of the electron transport chain due to mitochondrial DNA mutations and oncogenic pathway activation. Oxidative stress may further increase when metastasizing cancer cells enter the blood, a fluid with high levels of oxidants, including oxygen and iron. Most chemotherapeutics elevate intracellular levels of ROS. To maintain favorable redox homeostasis for tumor progression, cancer cells have evolved a complex redox system that strategically adjusts multiple antioxidants, including glutathione, NADPH, antioxidant enzymes, such as superoxide dismutases, catalases, glutathione peroxidases, glutathione reductase, glutathione S-transferases, thioredoxin, peroxiredoxins, sulfiredoxin, glutaredoxin, metallothionein-3, ferritin heavy chain, and dihydrodiol dehydrogenase. In addition, the tumor microenvironment and metabolic reprogramming may help cancer cells to overcome ROS-induced cellular stress.

This Special Issue is designed to bring together current research concerning the link between redox regulation and tumor initiation, proliferation, metastasis, autophagy, ferroptosis, metabolic reprogramming, tumor microenvironment, and therapeutic resistance.

Dr. Jie Zhang
Guest Editor

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Keywords

  • redox homeostasis
  • oxidative stress
  • ferroptosis
  • autophagy
  • cancer progression
  • cancer metastasis
  • cancer metabolism
  • tumor microenvironment
  • cancer therapy

Published Papers (2 papers)

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Research

29 pages, 11920 KiB  
Article
Redox Biomarkers and Matrix Remodeling Molecules in Ovarian Cancer
by Elżbieta Supruniuk, Marta Baczewska, Ewa Żebrowska, Mateusz Maciejczyk, Kamil Klaudiusz Lauko, Patrycja Dajnowicz-Brzezik, Patrycja Milewska, Paweł Knapp, Anna Zalewska and Adrian Chabowski
Antioxidants 2024, 13(2), 200; https://doi.org/10.3390/antiox13020200 - 04 Feb 2024
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Abstract
Ovarian cancer (OC) has emerged as the leading cause of death due to gynecological malignancies among women. Oxidative stress and metalloproteinases (MMPs) have been shown to influence signaling pathways and afflict the progression of carcinogenesis. Therefore, the assessment of matrix-remodeling and oxidative stress [...] Read more.
Ovarian cancer (OC) has emerged as the leading cause of death due to gynecological malignancies among women. Oxidative stress and metalloproteinases (MMPs) have been shown to influence signaling pathways and afflict the progression of carcinogenesis. Therefore, the assessment of matrix-remodeling and oxidative stress intensity can determine the degree of cellular injury and often the severity of redox-mediated chemoresistance. The study group comprised 27 patients with serous OC of which 18% were classified as Federation of Gynecology and Obstetrics (FIGO) stages I/II, while the rest were diagnosed grades III/IV. The control group comprised of 15 ovarian tissue samples. The results were compared with genetic data from The Cancer Genome Atlas. Nitro-oxidative stress, inflammation and apoptosis biomarkers were measured colorimetrically/fluorometrically or via real-time PCR in the primary ovarian tumor and healthy tissue. Stratification of patients according to FIGO stages revealed that high-grade carcinoma exhibited substantial alterations in redox balance, including the accumulation of protein glycoxidation and lipid peroxidation products. TCGA data demonstrated only limited prognostic usefulness of the studied genes. In conclusion, high-grade serous OC is associated with enhanced tissue oxidative/nitrosative stress and macromolecule damage that could not be overridden by the simultaneously augmented measures of antioxidant defense. Therefore, it can be assumed that tumor cells acquire adaptive mechanisms that enable them to withstand the potential toxic effects of elevated reactive oxygen species. Full article
(This article belongs to the Special Issue Redox Homeostasis in Cancers)
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27 pages, 17233 KiB  
Article
Monocarboxylate Transporter-1 (MCT1)-Mediated Lactate Uptake Protects Pancreatic Adenocarcinoma Cells from Oxidative Stress during Glutamine Scarcity Thereby Promoting Resistance against Inhibitors of Glutamine Metabolism
by Nourhane Ammar, Maya Hildebrandt, Claudia Geismann, Christian Röder, Timo Gemoll, Susanne Sebens, Ania Trauzold and Heiner Schäfer
Antioxidants 2023, 12(10), 1818; https://doi.org/10.3390/antiox12101818 - 30 Sep 2023
Viewed by 1341
Abstract
Metabolic compartmentalization of stroma-rich tumors, like pancreatic ductal adenocarcinoma (PDAC), greatly contributes to malignancy. This involves cancer cells importing lactate from the microenvironment (reverse Warburg cells) through monocarboxylate transporter-1 (MCT1) along with substantial phenotype alterations. Here, we report that the reverse Warburg phenotype [...] Read more.
Metabolic compartmentalization of stroma-rich tumors, like pancreatic ductal adenocarcinoma (PDAC), greatly contributes to malignancy. This involves cancer cells importing lactate from the microenvironment (reverse Warburg cells) through monocarboxylate transporter-1 (MCT1) along with substantial phenotype alterations. Here, we report that the reverse Warburg phenotype of PDAC cells compensated for the shortage of glutamine as an essential metabolite for redox homeostasis. Thus, oxidative stress caused by glutamine depletion led to an Nrf2-dependent induction of MCT1 expression in pancreatic T3M4 and A818-6 cells. Moreover, greater MCT1 expression was detected in glutamine-scarce regions within tumor tissues from PDAC patients. MCT1-driven lactate uptake supported the neutralization of reactive oxygen species excessively produced under glutamine shortage and the resulting drop in glutathione levels that were restored by the imported lactate. Consequently, PDAC cells showed greater survival and growth under glutamine depletion when utilizing lactate through MCT1. Likewise, the glutamine uptake inhibitor V9302 and glutaminase-1 inhibitor CB839 induced oxidative stress in PDAC cells, along with cell death and cell cycle arrest that were again compensated by MCT1 upregulation and forced lactate uptake. Our findings show a novel mechanism by which PDAC cells adapt their metabolism to glutamine scarcity and by which they develop resistance against anticancer treatments based on glutamine uptake/metabolism inhibition. Full article
(This article belongs to the Special Issue Redox Homeostasis in Cancers)
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