The Complex Interplay between Antioxidants and ROS in Cancer

Harris, Isaac S.; DeNicola, Gina M.

doi:10.1016/j.tcb.2020.03.002

Cited by 430 publications

(341 citation statements)

References 145 publications

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“…Mitochondrial ROS production in cells undergoing programmed cell death is complex, and it is known that the inhibition of ROS is specific to the antioxidant as well as the site of ROS generation ( Liu and Schubert, 2009 ). Recent studies have shown that there are different pools of ROS with differing functions in the same cells ( Cheung et al, 2016 ; Harris and DeNicola, 2020 ). Thus, the occurrence of staurosporine-induced apoptosis may require a particular oxidative environment, distinct from other apoptotic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine

2020

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Oxidative stress is known to contribute to the progression of apoptosis. Staurosporine is a broad-spectrum inducer of apoptosis, but its mechanism of action is not well understood. The goal of the present work was to elucidate the role of glutathione and reactive oxygen species (ROS) in the execution of staurosporine-induced apoptosis. HeLa cells were treated with staurosporine at 1 μM for up to 4 h. The concentration of glutathione, generation of ROS, and activation of caspase-3 were measured. The introduction of staurosporine significantly decreased the concentration of cellular glutathione and increased the presence of ROS after 3 h. These findings were concurrent with the activation of caspase-3. Interestingly, pre-treatment of cells with N-acetylcysteine, a precursor of glutathione, and a thiol antioxidant failed to block the depletion of glutathione, generation of ROS, and activation of caspase-3. Collectively, these results suggest that the cellular redox status may be one of the critical factors of the apoptotic pathway leading to caspase-3 activation by staurosporine.

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Section: Discussionmentioning

confidence: 99%

Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine

2020

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“…The group of antioxidants that repair or eliminate structural damage of biomolecules caused by free radicals is classified as the third line of antioxidant defense (de novo antioxidants). This group mainly includes DNA repair enzyme systems, lipase, and proteolytic enzymes which can repair damaged molecules [ 40 , 42 , 43 ]. Furthermore, there is another important adaptation mechanism may be regarded as the fourth defense line that is activated by reaction and production of free radicals inducing the formation and transport of appropriate antioxidant enzymes to the right site.…”

Section: Classification Of Antioxidantsmentioning

confidence: 99%

Antioxidant Supplementation in the Treatment of Neurotoxicity Induced by Platinum-Based Chemotherapeutics—A Review

Stanković

Selaković

Mihailović

et al. 2020

IJMS

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Cancer represents one of the most pernicious public health problems with a high mortality rate among patients worldwide. Chemotherapy is one of the major therapeutic approaches for the treatment of various malignancies. Platinum-based drugs (cisplatin, oxaliplatin, carboplatin, etc.) are highly effective chemotherapeutic drugs used for the treatment of several types of malignancies, but their application and dosage are limited by their toxic effects on various systems, including neurotoxicity. Simultaneously, researchers have tried to improve the survival rate and quality of life of cancer patients and decrease the toxicity of platinum-containing drugs by combining them with non-chemotherapy-based drugs, dietary supplements and/or antioxidants. Additionally, recent studies have shown that the root cause for the many side effects of platinum chemotherapeutics involves the production of reactive oxygen species (ROS) in naive cells. Therefore, suppression of ROS generation and their inactivation with antioxidants represents an appropriate approach for platinum drug-induced toxicities. The aim of this paper is to present an updated review of the protective effects of different antioxidant agents (vitamins, dietary antioxidants and supplements, medicaments, medicinal plants and their bioactive compounds) against the neurotoxicity induced by platinum-based chemotherapeutics. This review highlights the high potential of plant antioxidants as adjuvant strategies in chemotherapy with platinum drugs.

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“…The roles of NRF2 in tumorigenesis are context-dependent [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ], and likely influenced by different aspects of metabolism. The role of ROS metabolism is better defined, however, and has been well-characterized during cancer initiation, progression, and metastasis [ 23 ]. In healthy cells, activation of NRF2 promotes the transcription of anti-inflammatory and antioxidant genes that suppress the development of DNA damage and mutations that can initiate tumor formation [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, NRF2 supports the survival of transformed cells by protecting against oxidative damage to support their progression to more advanced-stage tumors. NRF2 loss can promote tumor cell migration and invasion through ROS-mediated epithelial-mesenchymal transition (EMT) [ 23 , 24 ]. NRF2 activation can also drive migration and invasion via the transcription factor BTB and CNC homology 1 (BACH1) in a heme metabolism-dependent manner [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Dissecting the Crosstalk between NRF2 Signaling and Metabolic Processes in Cancer

DeBlasi

DeNicola

2020

Cancers

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The transcription factor NRF2 (nuclear factor-erythroid 2 p45-related factor 2 or NFE2L2) plays a critical role in response to cellular stress. Following an oxidative insult, NRF2 orchestrates an antioxidant program, leading to increased glutathione levels and decreased reactive oxygen species (ROS). Mounting evidence now implicates the ability of NRF2 to modulate metabolic processes, particularly those at the interface between antioxidant processes and cellular proliferation. Notably, NRF2 regulates the pentose phosphate pathway, NADPH production, glutaminolysis, lipid and amino acid metabolism, many of which are hijacked by cancer cells to promote proliferation and survival. Moreover, deregulation of metabolic processes in both normal and cancer-based physiology can stabilize NRF2. We will discuss how perturbation of metabolic pathways, including the tricarboxylic acid (TCA) cycle, glycolysis, and autophagy can lead to NRF2 stabilization, and how NRF2-regulated metabolism helps cells deal with these metabolic stresses. Finally, we will discuss how the negative regulator of NRF2, Kelch-like ECH-associated protein 1 (KEAP1), may play a role in metabolism through NRF2 transcription-independent mechanisms. Collectively, this review will address the interplay between the NRF2/KEAP1 complex and metabolic processes.

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The Complex Interplay between Antioxidants and ROS in Cancer

Cited by 430 publications

References 145 publications

Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine

Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine

Antioxidant Supplementation in the Treatment of Neurotoxicity Induced by Platinum-Based Chemotherapeutics—A Review

Dissecting the Crosstalk between NRF2 Signaling and Metabolic Processes in Cancer

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