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Antioxidants
Special Issues
Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach
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Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: 31 August 2025 | Viewed by 10169

Special Issue Editor

Prof. Dr. Fábio Rodrigues Ferreira Seiva

E-Mail Website
Guest Editor
Institute of Bioscience, São Paulo State University, Botucatu, SP, Brazil
Interests: metabolic disorders; liver cancer; alternative treatments; energetic metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are in the process of preparing a new Special Issue entitled "Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach", and I would like to extend a cordial invitation to all those engaged in this dynamic field, spanning from bench research to clinical trials. Our aim is to publish well-designed studies that characterize, elucidate and corroborate the role of oxidative stress in carcinogenesis. We are also interested in papers that explore the potential application of alternative therapies that utilize antioxidants. The role of free radicals in the development of some types of tumors is well-established. Paradoxically, increased reactive species can be a valuable tool in combating tumor proliferation. Given the abundance of natural antioxidants found in nature, this area of research not only holds promise, but is also of paramount relevance and immediacy. In today's era, the various well-established "omics" release a large amount of experimental data. Studies using bioinformatics approaches are therefore also welcome, as well as articles addressing the interplay between oxidative stress, antioxidants, and cancer pathogenesis.

Prof. Dr. Fábio Rodrigues Ferreira Seiva
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • tumor biology
  • bioactive molecules
  • natural compounds
  • free radicals
  • alternative treatments

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Published Papers (5 papers)

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Research

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19 pages, 6539 KiB  
Article
In Silico Analysis of Non-Conventional Oxidative Stress-Related Enzymes and Their Potential Relationship with Carcinogenesis
by Fábio Rodrigues Ferreira Seiva, Maria Luisa Gonçalves Agneis, Matheus Ribas de Almeida, Wesley Ladeira Caputo, Milena Cremer de Souza, Karoliny Alves das Neves, Érika Novais Oliveira, Luis Antônio Justulin, Jr. and Luiz Gustavo de Almeida Chuffa
Antioxidants 2024, 13(11), 1279; https://doi.org/10.3390/antiox13111279 - 23 Oct 2024
Cited by 2 | Viewed by 1299
Abstract
Carcinogenesis is driven by complex molecular events, often involving key enzymes that regulate oxidative stress (OS). While classical enzymes such as SOD, catalase, and GPx have been extensively studied, other, non-classical oxidative stress-related enzymes (OSRE) may play critical roles in cancer progression. We [...] Read more.
Carcinogenesis is driven by complex molecular events, often involving key enzymes that regulate oxidative stress (OS). While classical enzymes such as SOD, catalase, and GPx have been extensively studied, other, non-classical oxidative stress-related enzymes (OSRE) may play critical roles in cancer progression. We aimed to explore the role of OSRE involved in an OS scenario and to assess their potential contribution to carcinogenesis in some of the most prevalent cancer types. Through data mining and bioinformatic analysis of gene and protein expression and mutation data, we identified OSRE with altered expression and mutations across cancer types. Functional pathways involving EGFR, MT-ND, GST, PLCG2, PRDX6, SRC, and JAK2 were investigated. Our findings reveal that enzymes traditionally considered peripheral to OS play significant roles in tumor progression. Those OSRE may contribute to cancer initiation and progression, as well as be involved with cancer hallmarks, such as EMT and invasion, proliferation, and ROS production. In addition, enzymes like SRC and JAK2 were found to have dual roles in both promoting ROS generation and being modulated by OS. OSRE also interact with key oncogenic signaling pathways, including Wnt/β-catenin and JAK2/STAT3, linking them to cancer aggressiveness and therapeutic resistance. Future research should focus on translating these findings into clinical applications, including the development of novel inhibitors or drugs targeting these non-classical enzymes. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach)
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32 pages, 10079 KiB  
Article
Deciphering the Landscape of GATA-Mediated Transcriptional Regulation in Gastric Cancer
by Rodiola Begolli, Anastasia Patouna, Periklis Vardakas, Anastasia Xagara, Kleanthi Apostolou, Demetrios Kouretas and Antonis Giakountis
Antioxidants 2024, 13(10), 1267; https://doi.org/10.3390/antiox13101267 - 18 Oct 2024
Cited by 1 | Viewed by 1760
Abstract
Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. [...] Read more.
Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. However, LS-TFs also govern important physiological roles, hindering their direct therapeutic targeting. Therefore, their downstream target genes are particularly interesting for developing cancer-specific molecular biomarkers or therapeutic agents. In this work, we couple inducible knockdown systems with chromatin immunoprecipitation and RNA-seq to thoroughly detect and characterize direct targets of GATA-mediated transcriptional regulation in gastric cancer cells. Our experimental and computational strategy provides evidence that both factors regulate the expression of several coding and non-coding RNAs that in turn mediate for their cancer-promoting phenotypes, including but not limited to cell cycle, apoptosis, ferroptosis, and oxidative stress response. Finally, the diagnostic and prognostic potential of four metagene signatures consisting of selected GATA4/6 target transcripts is evaluated in a multi-cancer panel of ~7000 biopsies from nineteen tumor types, revealing elevated specificity for gastrointestinal tumors. In conclusion, our integrated strategy uncovers the landscape of GATA-mediated coding and non-coding transcriptional regulation, providing insights regarding their molecular and clinical function in gastric cancer. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach)
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Review

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20 pages, 681 KiB  
Review
Hypoxia-Induced Reactive Oxygen Species: Their Role in Cancer Resistance and Emerging Therapies to Overcome It
by Eleicy Nathaly Mendoza, Maria Rosa Ciriolo and Fabio Ciccarone
Antioxidants 2025, 14(1), 94; https://doi.org/10.3390/antiox14010094 - 15 Jan 2025
Cited by 2 | Viewed by 1430
Abstract
Normal tissues typically maintain partial oxygen pressure within a range of 3–10% oxygen, ensuring homeostasis through a well-regulated oxygen supply and responsive vascular network. However, in solid tumors, rapid growth often outpaces angiogenesis, creating a hypoxic microenvironment that fosters tumor progression, altered metabolism [...] Read more.
Normal tissues typically maintain partial oxygen pressure within a range of 3–10% oxygen, ensuring homeostasis through a well-regulated oxygen supply and responsive vascular network. However, in solid tumors, rapid growth often outpaces angiogenesis, creating a hypoxic microenvironment that fosters tumor progression, altered metabolism and resistance to therapy. Hypoxic tumor regions experience uneven oxygen distribution with severe hypoxia in the core due to poor vascularization and high metabolic oxygen consumption. Cancer cells adapt to these conditions through metabolic shifts, predominantly relying on glycolysis, and by upregulating antioxidant defenses to mitigate reactive oxygen species (ROS)-induced oxidative damage. Hypoxia-induced ROS, resulting from mitochondrial dysfunction and enzyme activation, exacerbates genomic instability, tumor aggressiveness, and therapy resistance. Overcoming hypoxia-induced ROS cancer resistance requires a multifaceted approach that targets various aspects of tumor biology. Emerging therapeutic strategies target hypoxia-induced resistance, focusing on hypoxia-inducible factors, ROS levels, and tumor microenvironment subpopulations. Combining innovative therapies with existing treatments holds promise for improving cancer outcomes and overcoming resistance mechanisms. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach)
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42 pages, 1858 KiB  
Review
Vitamin C in the Management of Thyroid Cancer: A Highway to New Treatment?
by Francesca Gorini and Alessandro Tonacci
Antioxidants 2024, 13(10), 1242; https://doi.org/10.3390/antiox13101242 - 15 Oct 2024
Cited by 3 | Viewed by 2269
Abstract
Thyroid cancer (TC) is the most common endocrine malignancy, with an increased global incidence in recent decades, despite a substantially unchanged survival. While TC has an excellent overall prognosis, some types of TC are associated with worse patient outcomes, depending on the genetic [...] Read more.
Thyroid cancer (TC) is the most common endocrine malignancy, with an increased global incidence in recent decades, despite a substantially unchanged survival. While TC has an excellent overall prognosis, some types of TC are associated with worse patient outcomes, depending on the genetic setting. Furthermore, oxidative stress is related to more aggressive features of TC. Vitamin C, an essential nutrient provided with food or as a dietary supplement, is a well-known antioxidant and a scavenger of reactive oxygen species; however, at high doses, it can induce pro-oxidant effects, acting through multiple biological mechanisms that play a crucial role in killing cancer cells. Although experimental data and, less consistently, clinical studies, suggest the possibility of antineoplastic effects of vitamin C at pharmacological doses, the antitumor efficacy of this nutrient in TC remains at least partly unexplored. Therefore, this review discusses the current state of knowledge on the role of vitamin C, alone or in combination with other conventional therapies, in the management of TC, the mechanisms underlying this association, and the perspectives that may emerge in TC treatment strategies, and, also, in light of the development of novel functional foods useful to this extent, by implementing novel sensory analysis strategies. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach)
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17 pages, 1188 KiB  
Review
GLS and GLS2 Glutaminase Isoenzymes in the Antioxidant System of Cancer Cells
by Juan De los Santos-Jiménez, José A. Campos-Sandoval, Francisco J. Alonso, Javier Márquez and José M. Matés
Antioxidants 2024, 13(6), 745; https://doi.org/10.3390/antiox13060745 - 20 Jun 2024
Cited by 3 | Viewed by 2660
Abstract
A pathway frequently altered in cancer is glutaminolysis, whereby glutaminase (GA) catalyzes the main step as follows: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression [...] Read more.
A pathway frequently altered in cancer is glutaminolysis, whereby glutaminase (GA) catalyzes the main step as follows: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression patterns and can even perform opposing roles in cancer. GLS correlates with tumor growth and proliferation, while GLS2 can function as a context-dependent tumor suppressor. However, both isoenzymes have been described as essential molecules handling oxidant stress because of their involvement in glutathione production. We reviewed the literature to highlight the critical roles of GLS and GLS2 in restraining ROS and regulating both cellular signaling and metabolic stress due to their function as indirect antioxidant enzymes, as well as by modulating both reductive carboxylation and ferroptosis. Blocking GA activity appears to be a potential strategy in the dual activation of ferroptosis and inhibition of cancer cell growth in a ROS-mediated mechanism. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach)
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