scholarly journals Targeting the Redox Landscape in Cancer Therapy

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1706 ◽  
Author(s):  
Dilip Narayanan ◽  
Sana Ma ◽  
Dennis Özcelik
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Redox Homeostasis ◽  
Tumor Development ◽  
Cellular Level ◽  
Ros Production ◽  
Oxygen Species ◽  
Detoxifying Enzymes ◽  
Transport Chain ◽  
Hypoxic Tumor

Reactive oxygen species (ROS) are produced predominantly by the mitochondrial electron transport chain and by NADPH oxidases in peroxisomes and in the endoplasmic reticulum. The antioxidative defense counters overproduction of ROS with detoxifying enzymes and molecular scavengers, for instance, superoxide dismutase and glutathione, in order to restore redox homeostasis. Mutations in the redox landscape can induce carcinogenesis, whereas increased ROS production can perpetuate cancer development. Moreover, cancer cells can increase production of antioxidants, leading to resistance against chemo- or radiotherapy. Research has been developing pharmaceuticals to target the redox landscape in cancer. For instance, inhibition of key players in the redox landscape aims to modulate ROS production in order to prevent tumor development or to sensitize cancer cells in radiotherapy. Besides the redox landscape of a single cell, alternative strategies take aim at the multi-cellular level. Extracellular vesicles, such as exosomes, are crucial for the development of the hypoxic tumor microenvironment, and hence are explored as target and as drug delivery systems in cancer therapy. This review summarizes the current pharmaceutical and experimental interventions of the cancer redox landscape.

scholarly journals Reaction of carbon monoxide with cystathionine β-synthase: implications on drug efficacies in cancer chemotherapy

2020 ◽  
Vol 12 (4) ◽  
pp. 325-337
Author(s):  
Brian Kawahara ◽  
Suvajit Sen ◽  
Pradip K Mascharak
Keyword(s):  
Reactive Oxygen Species ◽  
Carbon Monoxide ◽  
Drug Resistance ◽  
Cancer Therapy ◽  
Antioxidant Capacity ◽  
Cancer Cells ◽  
Redox Homeostasis ◽  
Drug Effects ◽  
Oxygen Species ◽  
Treatment Regimens

Photo-activatable carbon monoxide (CO)-releasing molecules (photoCORMs), have recently provided help to identify the salutary effects of CO in human pathophysiology. Among them notable is the ability of CO to sensitize chemotherapeutic-resistant cancer cells. Findings from our group have shown CO to mitigate drug resistance in certain cancer cells by the inhibition of cystathionine β-synthase (CBS), a key regulator of redox homeostasis in the cell. Diminution of the antioxidant capacity of cancer cells leads to sensitization to reactive oxygen species-producing drugs like doxorubicin and paclitaxel upon cotreatment with CO as well as in mitigating the drug effects of cisplatin. We hypothesize that the development of CO delivery techniques for coadministration with existing cancer treatment regimens may ultimately improve clinical outcomes in cancer therapy.

scholarly journals Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 986
Author(s):  
Nada S. Aboelella ◽  
Caitlin Brandle ◽  
Timothy Kim ◽  
Zhi-Chun Ding ◽  
Gang Zhou
Keyword(s):  
Oxidative Stress ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Redox Homeostasis ◽  
Tumor Rejection ◽  
Oxygen Species ◽  
Antitumor Effects ◽  
Key Drivers ◽  
Cancer Immunotherapies ◽  
The Impact

It has been well-established that cancer cells are under constant oxidative stress, as reflected by elevated basal level of reactive oxygen species (ROS), due to increased metabolism driven by aberrant cell growth. Cancer cells can adapt to maintain redox homeostasis through a variety of mechanisms. The prevalent perception about ROS is that they are one of the key drivers promoting tumor initiation, progression, metastasis, and drug resistance. Based on this notion, numerous antioxidants that aim to mitigate tumor oxidative stress have been tested for cancer prevention or treatment, although the effectiveness of this strategy has yet to be established. In recent years, it has been increasingly appreciated that ROS have a complex, multifaceted role in the tumor microenvironment (TME), and that tumor redox can be targeted to amplify oxidative stress inside the tumor to cause tumor destruction. Accumulating evidence indicates that cancer immunotherapies can alter tumor redox to intensify tumor oxidative stress, resulting in ROS-dependent tumor rejection. Herein we review the recent progresses regarding the impact of ROS on cancer cells and various immune cells in the TME, and discuss the emerging ROS-modulating strategies that can be used in combination with cancer immunotherapies to achieve enhanced antitumor effects.

scholarly journals Somatic production of reactive oxygen species does not predict its production in sperm cells across Drosophila melanogaster lines

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Biz R. Turnell ◽  
Luisa Kumpitsch ◽  
Anne-Cécile Ribou ◽  
Klaus Reinhardt
Keyword(s):  
Reactive Oxygen Species ◽  
Drosophila Melanogaster ◽  
Reactive Oxygen ◽  
Future Research ◽  
Ros Production ◽  
Oxygen Species ◽  
Loss Of Function ◽  
Wild Type ◽  
Ros Scavenging ◽  
Transport Chain

Abstract Objective Sperm ageing has major evolutionary implications but has received comparatively little attention. Ageing in sperm and other cells is driven largely by oxidative damage from reactive oxygen species (ROS) generated by the mitochondria. Rates of organismal ageing differ across species and are theorized to be linked to somatic ROS levels. However, it is unknown whether sperm ageing rates are correlated with organismal ageing rates. Here, we investigate this question by comparing sperm ROS production in four lines of Drosophila melanogaster that have previously been shown to differ in somatic mitochondrial ROS production, including two commonly used wild-type lines and two lines with genetic modifications standardly used in ageing research. Results Somatic ROS production was previously shown to be lower in wild-type Oregon-R than in wild-type Dahomey flies; decreased by the expression of alternative oxidase (AOX), a protein that shortens the electron transport chain; and increased by a loss-of-function mutation in dj-1β, a gene involved in ROS scavenging. Contrary to predictions, we found no differences among these four lines in the rate of sperm ROS production. We discuss the implications of our results, the limitations of our study, and possible directions for future research.

scholarly journals Pleurotus albidus Modulates Mitochondrial Metabolism Disrupted by Hyperglycaemia in EA.hy926 Endothelial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Gabriela Gambato ◽  
Elisa Maria Pavão ◽  
Gabriela Chilanti ◽  
Roselei Claudete Fontana ◽  
Mirian Salvador ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Electron Transport Chain ◽  
Mitochondrial Disorder ◽  
Antioxidant Enzyme Activities ◽  
Ros Production ◽  
Oxygen Species ◽  
Transport Chain

Hyperglycaemia exacerbates the production of reactive oxygen species (ROS), contributing to the multiple complications associated with diabetes. Mitochondrial dysfunction is also known to be associated with diabetes. Therefore, the aim of this work was to study the effect of Pleurotus albidus extract on the mitochondrial dysfunction induced by hyperglycaemia in EA.hy926 endothelial cells. The results showed that P. albidus treatment prevented the increase in the activity of complex I of the electron transport chain and minimized the ROS production induced by hyperglycaemia. In addition, the extract minimized oxidative damage to lipids and proteins, caused an imbalance in the antioxidant enzyme activities of superoxide dismutase and catalase, and decreased the nitric oxide levels induced by hyperglycaemia. These data contribute to our understanding of the mitochondrial disorder induced by hyperglycaemia as well as establishing the conditions required to minimize these alterations.

scholarly journals Redox Homeostasis and Metabolism in Cancer: A Complex Mechanism and Potential Targeted Therapeutics

2020 ◽  
Vol 21 (9) ◽  
pp. 3100 ◽  
Author(s):  
Alia Ghoneum ◽  
Ammar Yasser Abdulfattah ◽  
Bailey Olivia Warren ◽  
Junjun Shu ◽  
Neveen Said
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Metabolic Pathways ◽  
Redox Homeostasis ◽  
Ros Production ◽  
Biological Processes ◽  
Survival Pathways ◽  
Oncogenic Mutations ◽  
And Oxidative Stress ◽  
Shed Light

Reactive Oxygen Species or “ROS” encompass several molecules derived from oxygen that can oxidize other molecules and subsequently transition rapidly between species. The key roles of ROS in biological processes are cell signaling, biosynthetic processes, and host defense. In cancer cells, increased ROS production and oxidative stress are instigated by carcinogens, oncogenic mutations, and importantly, metabolic reprograming of the rapidly proliferating cancer cells. Increased ROS production activates myriad downstream survival pathways that further cancer progression and metastasis. In this review, we highlight the relation between ROS, the metabolic programing of cancer, and stromal and immune cells with emphasis on and the transcription machinery involved in redox homeostasis, metabolic programing and malignant phenotype. We also shed light on the therapeutic targeting of metabolic pathways generating ROS as we investigate: Orlistat, Biguandes, AICAR, 2 Deoxyglucose, CPI-613, and Etomoxir.

scholarly journals Integration of intracellular telomerase monitoring by electrochemiluminescence technology and targeted cancer therapy by reactive oxygen species

2017 ◽  
Vol 8 (12) ◽  
pp. 8025-8029 ◽  
Author(s):  
Huairong Zhang ◽  
Binxiao Li ◽  
Zhaomei Sun ◽  
Hong Zhou ◽  
Shusheng Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Targeted Cancer Therapy ◽  
High Efficacy

ROS and polyluminol–Pt NPs were used for intracellular telomerase detection and to induce apoptosis in HL-60 cancer cells with high efficacy.

scholarly journals Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 109 ◽  
Author(s):  
Maria Mrakovcic ◽  
Leopold F. Fröhlich
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Tumor Development ◽  
Therapy Resistance ◽  
Histone Deacetylation ◽  
Apoptosis Resistance ◽  
Drug Induced ◽  
Protective Function ◽  
Molecular Determinants

Histone deacetylation inhibitors (HDACi) offer high potential for future cancer therapy as they can re-establish the expression of epigenetically silenced cell death programs. HDACi-induced autophagy offers the possibility to counteract the frequently present apoptosis-resistance as well as stress conditions of cancer cells. Opposed to the function of apoptosis and necrosis however, autophagy activated in cancer cells can engage in a tumor-suppressive or tumor-promoting manner depending on mostly unclarified factors. As a physiological adaption to apoptosis resistance in early phases of tumorigenesis, autophagy seems to resume a tumorsuppressive role that confines tumor necrosis and inflammation or even induces cell death in malignant cells. During later stages of tumor development, chemotherapeutic drug-induced autophagy seems to be reprogrammed by the cancer cell to prevent its elimination and support tumor progression. Consistently, HDACi-mediated activation of autophagy seems to exert a protective function that prevents the induction of apoptotic or necrotic cell death in cancer cells. Thus, resistance to HDACi-induced cell death is often encountered in various types of cancer as well. The current review highlights the different mechanisms of HDACi-elicited autophagy and corresponding possible molecular determinants of therapeutic resistance in cancer.

π-π Conjugation Promoted Nanocatalysis for Cancer Therapy Based on Covalent Organic Framework

2021 ◽  
Author(s):  
Shuncheng Yao ◽  
Xingru Zhao ◽  
Xingyi Wan ◽  
Xueyu Wang ◽  
Tian Huang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Therapy ◽  
Oxidative Damage ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Covalent Organic Framework ◽  
Organic Framework

The production of reactive oxygen species (ROS) to elicit lethal cellular oxidative damage is an attractive pathway to kill cancer, but it is still hindered by the low ROS production...

scholarly journals Parenteral Succinate Reduces Systemic ROS Production in Septic Rats, but It Does Not Reduce Creatinine Levels

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Sebastián P. Chapela ◽  
Isabel Burgos ◽  
Christian Congost ◽  
Romina Canzonieri ◽  
Alexis Muryan ◽  
...  
Keyword(s):  
Complex I ◽  
Electron Transport Chain ◽  
Cecal Ligation ◽  
Multiple Organ ◽  
Sepsis Group ◽  
Control Group ◽  
Ros Production ◽  
Oxygen Species ◽  
Cecal Ligation And Puncture ◽  
Transport Chain

In sepsis, reactive oxygen species (ROS) production is increased. This process takes place mainly within the electron transport chain. ROS production is part of the pathophysiology of multiple organ failure in sepsis. Succinate yields Dihydroflavine-Adenine Dinucleotide (FADH2), which enters the chain through complex II, avoiding complex I, through which electrons are lost. The aim of this work is to determine if parenteral succinate reduces systemic ROS production and improves kidney function. Rats with cecal ligation and puncture were used as model of sepsis, and 4 groups were made: Control group; Succinate group, which only received parenteral succinate; Sepsis group; and Sepsis which received parenteral succinate. Systemic ROS are measured 24 hours after the procedure. Rats subjected to cecal puncture treated with succinate had less systemic ROS than Septic untreated rats (p=0.007), while there were no differences in creatinine levels (p=0.07). There was no correlation between creatinine and systemic ROS levels (p=0.3). We concluded that parenteral succinate reduces ROS levels, but it does not reduce creatinine levels. Since there is no correlation between both levels, the processes would not be related.

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