scholarly journals Role of Reductive versus Oxidative Stress in Tumor Progression and Anticancer Drug Resistance

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 758
Author(s):  
Kyung-Soo Chun ◽  
Do-Hee Kim ◽  
Young-Joon Surh
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathways ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Therapy Resistance ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cellular Redox ◽  
Reductive Stress

Redox homeostasis is not only essential for the maintenance of normal physiological functions, but also plays an important role in the growth, survival, and therapy resistance of cancer cells. Altered redox balance and consequent disruption of redox signaling are implicated in the proliferation and progression of cancer cells and their resistance to chemo- and radiotherapy. The nuclear factor erythroid 2 p45-related factor (Nrf2) is the principal stress-responsive transcription factor that plays a pivotal role in maintaining cellular redox homeostasis. Aberrant Nrf2 overactivation has been observed in many cancerous and transformed cells. Uncontrolled amplification of Nrf2-mediated antioxidant signaling results in reductive stress. Some metabolic pathways altered due to reductive stress have been identified as major contributors to tumorigenesis. This review highlights the multifaceted role of reductive stress in cancer development and progression.

scholarly journals Metabolic Regulation of Redox Balance in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 955 ◽  
Author(s):  
Vinee Purohit ◽  
Diane M. Simeone ◽  
Costas A. Lyssiotis
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Regulation ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Tumor Evolution ◽  
Ros Production ◽  
Oxygen Species ◽  
Partial Reduction ◽  
Dna Mutations

Reactive oxygen species (ROS) are chemically active free radicals produced by partial reduction of oxygen that can activate discrete signaling pathways or disrupt redox homeostasis depending on their concentration. ROS interacts with biomolecules, including DNA, and can cause mutations that can transform normal cells into cancer cells. Furthermore, certain cancer-causing mutations trigger alterations in cellular metabolism that can increase ROS production, resulting in genomic instability, additional DNA mutations, and tumor evolution. To prevent excess ROS-mediated toxicity, cancer-causing mutations concurrently activate pathways that manage this oxidative burden. Hence, an understanding of the metabolic pathways that regulate ROS levels is imperative for devising therapies that target tumor cells. In this review, we summarize the dual role of metabolism as a generator and inhibitor of ROS in cancer and discuss current strategies to target the ROS axis.

scholarly journals Role of Hydrogen Sulfide in NRF2- and Sirtuin-Dependent Maintenance of Cellular Redox Balance

Antioxidants ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 129 ◽  
Author(s):  
Tiziana Corsello ◽  
Narayana Komaravelli ◽  
Antonella Casola
Keyword(s):  
Hydrogen Sulfide ◽  
Redox Homeostasis ◽  
Antioxidant Properties ◽  
Redox Balance ◽  
Cellular Redox ◽  
Endogenous Production ◽  
Organ Specific ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Antioxidant Effects

Hydrogen sulfide (H2S) has arisen as a critical gasotransmitter signaling molecule modulating cellular biological events related to health and diseases in heart, brain, liver, vascular systems and immune response. Three enzymes mediate the endogenous production of H2S: cystathione β-synthase (CBS), cystathione γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). CBS and CSE localizations are organ-specific. 3-MST is a mitochondrial and cytosolic enzyme. The generation of H2S is firmly regulated by these enzymes under normal physiological conditions. Recent studies have highlighted the role of H2S in cellular redox homeostasis, as it displays significant antioxidant properties. H2S exerts antioxidant effects through several mechanisms, such as quenching reactive oxygen species (ROS) and reactive nitrogen species (RNS), by modulating cellular levels of glutathione (GSH) and thioredoxin (Trx-1) or increasing expression of antioxidant enzymes (AOE), by activating the transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2). H2S also influences the activity of the histone deacetylase protein family of sirtuins, which plays an important role in inhibiting oxidative stress in cardiomyocytes and during the aging process by modulating AOE gene expression. This review focuses on the role of H2S in NRF2 and sirtuin signaling pathways as they are related to cellular redox homeostasis.

scholarly journals The Role of Nrf2 in Skeletal Muscle on Exercise Capacity

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1712
Author(s):  
Yu Kitaoka
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Exercise Physiology ◽  
Redox Homeostasis ◽  
Muscle Metabolism ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nitrogen Species ◽  
Special Issue

Nuclear factor erythroid 2-related factor 2 Nfe2l2 (Nrf2) is believed to play a crucial role in protecting cells against oxidative stress. In addition to its primary function of maintaining redox homeostasis, there is emerging evidence that Nrf2 is also involved in energy metabolism. In this review, we briefly discuss the role of Nrf2 in skeletal muscle metabolism from the perspective of exercise physiology. This article is part of a special issue “Mitochondrial Function, Reactive Oxygen/Nitrogen Species and Skeletal Muscle” edited by Håkan Westerblad and Takashi Yamada.

scholarly journals Biotechnologically-Produced Myconoside and Calceolarioside E Induce Nrf2 Expression in Neutrophils

2021 ◽  
Vol 22 (4) ◽  
pp. 1759
Author(s):  
Kristiana M. Amirova ◽  
Petya A. Dimitrova ◽  
Andrey S. Marchev ◽  
Slaveya V. Krustanova ◽  
Svetlana D. Simova ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Acid Methyl Ester ◽  
Redox Balance ◽  
Biologically Active ◽  
Redox Activity ◽  
Related Factor ◽  
Cellular Redox ◽  
Nrf2 Expression

The pathological manifestation of various diseases can be suppressed by the activation of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a transcriptional regulator of the cellular redox balance. Haberlea rhodopensis Friv. is a resurrection plant species endemic for Bulgaria, containing biologically active phenylethanoid glycosides that might possess antioxidant or redox activity. This study aimed to analyze the metabolic profile of in vitro cultured H. rhodopensis and to identify molecules that increase Nrf2 expression in bone marrow neutrophils. Fractions B, D, and E containing myconoside, or myconoside and calceolarioside E in ratios 1:0.6 and 0.25:1 were found to be the most active ones. Fraction B (200 µg/mL) improved neutrophil survival and strongly increased the Nrf2 intracellular level, while D and E, as well as, myconoside and calceolarioside E at the same ratios had a superior effect. Calceolarioside E (32 µg/mL) had stronger activity than myconoside, the effect of which was very similar to that of 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me), used as a positive control. These data indicate that both molecules, used alone or in combination have stimulatory activity on the endogenous Nrf2 level, indicating their therapeutic potential to regulate the cellular redox homeostasis oxidative stress-associated pathologies.

scholarly journals Mitochondrial Sirtuins in Reproduction

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1047
Author(s):  
Giovanna Di Emidio ◽  
Stefano Falone ◽  
Paolo Giovanni Artini ◽  
Fernanda Amicarelli ◽  
Anna Maria D’Alessandro ◽  
...  
Keyword(s):  
Stress Responses ◽  
Metabolic Pathways ◽  
Redox Balance ◽  
Antioxidant Defenses ◽  
Metabolic Abnormalities ◽  
Female Reproduction ◽  
Mitochondrial Dysfunctions ◽  
Early Embryos ◽  
The Relationship

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.

scholarly journals Differential Expression of Peroxisomal Proteins in Distinct Types of Parotid Gland Tumors

2021 ◽  
Vol 22 (15) ◽  
pp. 7872
Author(s):  
Malin Tordis Meyer ◽  
Christoph Watermann ◽  
Thomas Dreyer ◽  
Steffen Wagner ◽  
Claus Wittekindt ◽  
...  
Keyword(s):  
Redox Balance ◽  
Matrix Proteins ◽  
Parotid Tumor ◽  
Gene Expressions ◽  
Tissue Samples ◽  
Cellular Redox ◽  
Tumor Subtypes ◽  
Parotid Tumors ◽  
Aggressive Tumors

Salivary gland cancers are rare but aggressive tumors that have poor prognosis and lack effective cure. Of those, parotid tumors constitute the majority. Functioning as metabolic machinery contributing to cellular redox balance, peroxisomes have emerged as crucial players in tumorigenesis. Studies on murine and human cells have examined the role of peroxisomes in carcinogenesis with conflicting results. These studies either examined the consequences of altered peroxisomal proliferators or compared their expression in healthy and neoplastic tissues. None, however, examined such differences exclusively in human parotid tissue or extended comparison to peroxisomal proteins and their associated gene expressions. Therefore, we examined differences in peroxisomal dynamics in parotid tumors of different morphologies. Using immunofluorescence and quantitative PCR, we compared the expression levels of key peroxisomal enzymes and proliferators in healthy and neoplastic parotid tissue samples. Three parotid tumor subtypes were examined: pleomorphic adenoma, mucoepidermoid carcinoma and acinic cell carcinoma. We observed higher expression of peroxisomal matrix proteins in neoplastic samples with exceptional down regulation of certain enzymes; however, the degree of expression varied between tumor subtypes. Our findings confirm previous experimental results on other organ tissues and suggest peroxisomes as possible therapeutic targets or markers in all or certain subtypes of parotid neoplasms.

scholarly journals Anti-Carcinogenic Glucosinolates in Cruciferous Vegetables and Their Antagonistic Effects on Prevention of Cancers

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2983 ◽  
Author(s):  
Prabhakaran Soundararajan ◽  
Jung Kim
Keyword(s):  
Antagonistic Activity ◽  
Antagonistic Effect ◽  
Side Chain ◽  
Cruciferous Vegetables ◽  
Related Factor ◽  
Nuclear Factor ◽  
Naturally Occurring ◽  
Therapeutic Properties ◽  
Responsive Element

Glucosinolates (GSL) are naturally occurring β-d-thioglucosides found across the cruciferous vegetables. Core structure formation and side-chain modifications lead to the synthesis of more than 200 types of GSLs in Brassicaceae. Isothiocyanates (ITCs) are chemoprotectives produced as the hydrolyzed product of GSLs by enzyme myrosinase. Benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and sulforaphane ([1-isothioyanato-4-(methyl-sulfinyl) butane], SFN) are potential ITCs with efficient therapeutic properties. Beneficial role of BITC, PEITC and SFN was widely studied against various cancers such as breast, brain, blood, bone, colon, gastric, liver, lung, oral, pancreatic, prostate and so forth. Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor limits the tumor progression. Induction of ARE (antioxidant responsive element) and ROS (reactive oxygen species) mediated pathway by Nrf2 controls the activity of nuclear factor-kappaB (NF-κB). NF-κB has a double edged role in the immune system. NF-κB induced during inflammatory is essential for an acute immune process. Meanwhile, hyper activation of NF-κB transcription factors was witnessed in the tumor cells. Antagonistic activity of BITC, PEITC and SFN against cancer was related with the direct/indirect interaction with Nrf2 and NF-κB protein. All three ITCs able to disrupts Nrf2-Keap1 complex and translocate Nrf2 into the nucleus. BITC have the affinity to inhibit the NF-κB than SFN due to the presence of additional benzyl structure. This review will give the overview on chemo preventive of ITCs against several types of cancer cell lines. We have also discussed the molecular interaction(s) of the antagonistic effect of BITC, PEITC and SFN with Nrf2 and NF-κB to prevent cancer.

scholarly journals Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2

Nutrients ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 223 ◽  
Author(s):  
Masutaka Furue ◽  
Hiroshi Uchi ◽  
Chikage Mitoma ◽  
Akiko Hashimoto-Hachiya ◽  
Takahito Chiba ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptors ◽  
Related Factor ◽  
Nuclear Factor ◽  
Healthy Skin ◽  
Aryl Hydrocarbon
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