Oxidative Stress and Redox Regulation in Hematological Malignancies: Pro-oxidant Strategy or Antioxidant Approach?

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 August 2023) | Viewed by 8052

Special Issue Editor


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Guest Editor
Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, Italy
Interests: blood disease; hematological malignancies; myeloma; lymphoma; leukemia; platelets; hematology
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Special Issue Information

Dear Colleagues,

Redox homeostasis is a critical element of hematological malignancies and oxidative stress affects most, if not all, aspects of cell proliferation and chemoresistance. Abnormal oxidative stress is present in clonal cells and in normal bone marrow cells during a hematological malignancy. The increase in oxidative stress, if not adequately compensated by an antioxidant defense, has a significant impact on these diseases, inducing many inflammatory processes linked to DNA mutation and tumor development.

This Special Issue aims to stimulate discussion and highlight the latest developments in understanding  how and why oxidative stress occurs in tumor cells and the mechanisms linking altered redox system to tumorigenesis. Understanding how oxidative stress influences the behavior of neoplastic cells could support the development of new therapeutical strategies and drugs targeting metabolic pathways to destroy tumour cells.

We welcome reviews and original research articles that cover any pertinent topic in the fields mentioned above, both basic and clinical aspects. Particularly awaited will be the works aimed at evaluating the use of new methodologies useful for modifying oxidative stress such as nanotechnologies and the employ of cold atmospheric plasma.

Dr. Alessandro Allegra
Guest Editor

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Keywords

  • oxidative stress
  • antioxidant
  • ROS
  • mitochondria
  • hematological malignancy
  • tumoral microenvironment
  • genomic instability
  • DNA damage
  • myeloma
  • lymphoma
  • leukemia

Published Papers (4 papers)

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Research

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0 pages, 6822 KiB  
Article
Effects of Deacetylase Inhibition on the Activation of the Antioxidant Response and Aerobic Metabolism in Cellular Models of Fanconi Anemia
by Nadia Bertola, Stefano Regis, Silvia Bruno, Andrea Nicola Mazzarello, Martina Serra, Michela Lupia, Federica Sabatini, Fabio Corsolini, Silvia Ravera and Enrico Cappelli
Antioxidants 2023, 12(5), 1100; https://doi.org/10.3390/antiox12051100 - 15 May 2023
Cited by 2 | Viewed by 1432
Abstract
Fanconi anemia (FA) is a rare genetic disease characterized by a dysfunctional DNA repair and an oxidative stress accumulation due to defective mitochondrial energy metabolism, not counteracted by endogenous antioxidant defenses, which appear down-expressed compared to the control. Since the antioxidant response lack [...] Read more.
Fanconi anemia (FA) is a rare genetic disease characterized by a dysfunctional DNA repair and an oxidative stress accumulation due to defective mitochondrial energy metabolism, not counteracted by endogenous antioxidant defenses, which appear down-expressed compared to the control. Since the antioxidant response lack could depend on the hypoacetylation of genes coding for detoxifying enzymes, we treated lymphoblasts and fibroblasts mutated for the FANC-A gene with some histone deacetylase inhibitors (HDACi), namely, valproic acid (VPA), beta-hydroxybutyrate (OHB), and EX527 (a Sirt1 inhibitor), under basal conditions and after hydrogen peroxide addition. The results show that VPA increased catalase and glutathione reductase expression and activity, corrected the metabolic defect, lowered lipid peroxidation, restored the mitochondrial fusion and fission balance, and improved mitomycin survival. In contrast, OHB, despite a slight increase in antioxidant enzyme expressions, exacerbated the metabolic defect, increasing oxidative stress production, probably because it also acts as an oxidative phosphorylation metabolite, while EX527 showed no effect. In conclusion, the data suggest that VPA could be a promising drug to modulate the gene expression in FA cells, confirming that the antioxidant response modulation plays a pivotal in FA pathogenesis as it acts on both oxidative stress levels and the mitochondrial metabolism and dynamics quality. Full article
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Review

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12 pages, 1031 KiB  
Review
Harnessing Redox Disruption to Treat Human Herpesvirus 8 (HHV-8) Related Malignancies
by Adélie Gothland, Aude Jary, Philippe Grange, Valentin Leducq, Laurianne Beauvais-Remigereau, Nicolas Dupin, Anne-Geneviève Marcelin and Vincent Calvez
Antioxidants 2023, 12(1), 84; https://doi.org/10.3390/antiox12010084 - 30 Dec 2022
Cited by 3 | Viewed by 1835
Abstract
Reprogrammed metabolism is regarded as a hallmark of cancer and offers a selective advantage to tumor cells during carcinogenesis. The redox equilibrium is necessary for growth, spread and the antioxidant pathways are boosted following Reactive Oxygen Species (ROS) production to prevent cell damage [...] Read more.
Reprogrammed metabolism is regarded as a hallmark of cancer and offers a selective advantage to tumor cells during carcinogenesis. The redox equilibrium is necessary for growth, spread and the antioxidant pathways are boosted following Reactive Oxygen Species (ROS) production to prevent cell damage in tumor cells. Human herpesvirus 8 (HHV-8), the etiologic agent of Kaposi sarcoma KS and primary effusion lymphoma (PEL), is an oncogenic virus that disrupts cell survival-related molecular signaling pathways leading to immune host evasion, cells growths, angiogenesis and inflammatory tumor-environment. We recently reported that primaquine diphosphate causes cell death by apoptosis in HHV-8 infected PEL cell lines in vivo and exhibits therapeutic anti-tumor activity in mice models and advanced KS. Our findings also suggest that the primaquine-induced apoptosis in PEL cells is mostly influenced by ROS production and targeting the redox balance could be a new approach to treat HHV-8 related diseases. In this review, we summarized the knowledge about the influence of ROS in cancer development; more specifically, the proof of evidence from our work and from the literature that redox pathways are important for the development of HHV-8 pathologies. Full article
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22 pages, 2153 KiB  
Review
Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?
by Alessandro Allegra, Alessandro Tonacci, Laura Giordano, Caterina Musolino and Sebastiano Gangemi
Antioxidants 2022, 11(9), 1696; https://doi.org/10.3390/antiox11091696 - 29 Aug 2022
Cited by 6 | Viewed by 1836
Abstract
Redox adaptation is essential for human health, as the physiological quantities of non-radical reactive oxygen species operate as the main second messengers to regulate normal redox reactions by controlling several sensors. An abnormal increase reactive oxygen species, called oxidative stress, induces biological injury. [...] Read more.
Redox adaptation is essential for human health, as the physiological quantities of non-radical reactive oxygen species operate as the main second messengers to regulate normal redox reactions by controlling several sensors. An abnormal increase reactive oxygen species, called oxidative stress, induces biological injury. For this reason, variations in oxidative stress continue to receive consideration as a possible approach to treat leukemic diseases. However, the intricacy of redox reactions and their effects might be a relevant obstacle; consequently, and alongside approaches aimed at increasing oxidative stress in neoplastic cells, antioxidant strategies have also been suggested for the same purpose. The present review focuses on the molecular processes of anomalous oxidative stress in acute myeloid and acute lymphoblastic leukemias as well as on the oxidative stress-determined pathways implicated in leukemogenic development. Furthermore, we review the effect of chemotherapies on oxidative stress and the possibility that their pharmacological effects might be increased by modifying the intracellular redox equilibrium through a pro-oxidant approach or an antioxidant strategy. Finally, we evaluated the prospect of varying oxidative stress as an efficacious modality to destroy chemoresistant cells using new methodologies. Altering redox conditions may be advantageous for inhibiting genomic variability and the eradication of leukemic clones will promote the treatment of leukemic disease. Full article
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19 pages, 1080 KiB  
Review
Cold Atmospheric Plasma Targeting Hematological Malignancies: Potentials and Problems of Clinical Translation
by Sebastiano Gangemi, Claudia Petrarca, Alessandro Tonacci, Mario Di Gioacchino, Caterina Musolino and Alessandro Allegra
Antioxidants 2022, 11(8), 1592; https://doi.org/10.3390/antiox11081592 - 17 Aug 2022
Cited by 10 | Viewed by 2242
Abstract
Cold atmospheric plasma is an ionized gas produced near room temperature; it generates reactive oxygen species and nitrogen species and induces physical changes, including ultraviolet, radiation, thermal, and electromagnetic effects. Several studies showed that cold atmospheric plasma could effectively provoke death in a [...] Read more.
Cold atmospheric plasma is an ionized gas produced near room temperature; it generates reactive oxygen species and nitrogen species and induces physical changes, including ultraviolet, radiation, thermal, and electromagnetic effects. Several studies showed that cold atmospheric plasma could effectively provoke death in a huge amount of cell types, including neoplastic cells, via the induction of apoptosis, necrosis, and autophagy. This technique seems able to destroy tumor cells by disturbing their more susceptible redox equilibrium with respect to normal cells, but it is also able to cause immunogenic cell death by enhancing the immune response, to decrease angiogenesis, and to provoke genetic and epigenetics mutations. Solutions activated by cold gas plasma represent a new modality for treatment of less easily reached tumors, or hematological malignancies. Our review reports on accepted knowledge of cold atmospheric plasma’s effect on hematological malignancies, such as acute and chronic myeloid leukemia and multiple myeloma. Although relevant progress was made toward understanding the underlying mechanisms concerning the efficacy of cold atmospheric plasma in hematological tumors, there is a need to determine both guidelines and safety limits that guarantee an absence of long-term side effects. Full article
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