scholarly journals Oxidative Stress-Inducing Anticancer Therapies: Taking a Closer Look at Their Immunomodulating Effects

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1188
Author(s):  
Jinthe Van Loenhout ◽  
Marc Peeters ◽  
Annemie Bogaerts ◽  
Evelien Smits ◽  
Christophe Deben
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Treatment Strategies ◽  
Redox Balance ◽  
Cellular Responses ◽  
Anticancer Therapy ◽  
Treatment Modalities ◽  
Oxygen Species ◽  
Novel Target ◽  
High Level

Cancer cells are characterized by higher levels of reactive oxygen species (ROS) compared to normal cells as a result of an imbalance between oxidants and antioxidants. However, cancer cells maintain their redox balance due to their high antioxidant capacity. Recently, a high level of oxidative stress is considered a novel target for anticancer therapy. This can be induced by increasing exogenous ROS and/or inhibiting the endogenous protective antioxidant system. Additionally, the immune system has been shown to be a significant ally in the fight against cancer. Since ROS levels are important to modulate the antitumor immune response, it is essential to consider the effects of oxidative stress-inducing treatments on this response. In this review, we provide an overview of the mechanistic cellular responses of cancer cells towards exogenous and endogenous ROS-inducing treatments, as well as the indirect and direct antitumoral immune effects, which can be both immunostimulatory and/or immunosuppressive. For future perspectives, there is a clear need for comprehensive investigations of different oxidative stress-inducing treatment strategies and their specific immunomodulating effects, since the effects cannot be generalized over different treatment modalities. It is essential to elucidate all these underlying immune effects to make oxidative stress-inducing treatments effective anticancer therapy.

scholarly journals Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production

2007 ◽  
Vol 402 (2) ◽  
pp. 219-227 ◽  
Author(s):  
Yoshihito Iuchi ◽  
Futoshi Okada ◽  
Kunishige Onuma ◽  
Tadashi Onoda ◽  
Hironobu Asao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox Balance ◽  
Oxidative Modification ◽  
Autoimmune Response ◽  
Oxygen Species ◽  
Autoantibody Production ◽  
Oxidative Modification Of Proteins ◽  
High Level ◽  
Continuous Destruction

Reactive oxygen species are involved in the aging process and diseases. Despite the important role of Cu/Zn SOD (superoxide dismutase) encoded by SOD1, SOD1−/− mice appear to grow normally under conventional breeding conditions. In the present paper we report on a novel finding showing a distinct connection between oxidative stress in erythrocytes and the production of autoantibodies against erythrocytes in SOD1−/− mice. Evidence is presented to show that SOD1 is primarily required for maintaining erythrocyte lifespan by suppressing oxidative stress. A SOD1 deficiency led to an increased erythrocyte vulnerability by the oxidative modification of proteins and lipids, resulting in anaemia and compensatory activation of erythropoiesis. The continuous destruction of oxidized erythrocytes appears to induce the formation of autoantibodies against certain erythrocyte components, e.g. carbonic anhydrase II, and the immune complex is deposited in the glomeruli. The administration of an antioxidant, N-acetylcysteine, suppressed erythrocyte oxidation, ameliorated the anaemia, and inhibited the production of autoantibodies. These data imply that a high level of oxidative stress in erythrocytes increases the production of autoantibodies, possibly leading to an autoimmune response, and that the intake of antioxidants would prevent certain autoimmune responses by maintaining an appropriate redox balance in erythrocytes.

scholarly journals Understanding of ROS-Inducing Strategy in Anticancer Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Su Ji Kim ◽  
Hyun Soo Kim ◽  
Young Rok Seo
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Biological Response ◽  
Buthionine Sulfoximine ◽  
Redox Balance ◽  
Anticancer Therapy ◽  
Therapeutic Effects

Redox homeostasis is essential for the maintenance of diverse cellular processes. Cancer cells have higher levels of reactive oxygen species (ROS) than normal cells as a result of hypermetabolism, but the redox balance is maintained in cancer cells due to their marked antioxidant capacity. Recently, anticancer therapies that induce oxidative stress by increasing ROS and/or inhibiting antioxidant processes have received significant attention. The acceleration of accumulative ROS disrupts redox homeostasis and causes severe damage in cancer cells. In this review, we describe ROS-inducing cancer therapy and the anticancer mechanism employed by prooxidative agents. To understand the comprehensive biological response to certain prooxidative anticancer drugs such as 2-methoxyestradiol, buthionine sulfoximine, cisplatin, doxorubicin, imexon, and motexafin gadolinium, we propose and visualize the drug-gene, drug-cell process, and drug-disease interactions involved in oxidative stress induction and antioxidant process inhibition as well as specific side effects of these drugs using pathway analysis with a big data-based text-mining approach. Our review will be helpful to improve the therapeutic effects of anticancer drugs by providing information about biological changes that occur in response to prooxidants. For future directions, there is still a need for pharmacogenomic studies on prooxidative agents as well as the molecular mechanisms underlying the effects of the prooxidants and/or antioxidant-inhibitor agents for effective anticancer therapy through selective killing of cancer cells.

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.

Different Chilling-Induced Symptoms and the Underlying Oxidative Stress and Antioxidative Defense in the Exocarp and Mesocarp of Immature Sponge Gourd (Luffa cylindrica) Fruit

2021 ◽  
Author(s):  
Pichaya Chuenchom ◽  
Sompoch Noichinda ◽  
Kitti Bodhipadma ◽  
Chalermchai Wongs-Aree ◽  
David W. M. Leung
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Considerable Increase ◽  
Chilling Injury ◽  
Oxygen Species ◽  
Antioxidative Defense ◽  
Sponge Gourd ◽  
Lower Temperature ◽  
High Level ◽  
The Relationship

Immature sponge gourd fruit is consumed as a vegetable with a limited shelf life. Although cold storage is a simple and powerful tool for maintaining postharvest fruit quality, storage at a low temperature may not be appropriate for vegetables as some chilling injury (CI) of the immature sponge gourd fruit may occur. Therefore, this research aimed to elucidate the relationship between CI, oxidative stress, and the antioxidative defense mechanisms in the exocarp and mesocarp of immature sponge gourd fruit. After storage at 5°C for 6 days, visual CI symptoms, including browning and surface pitting, were found in the peel (exocarp) but not in the mesocarp. There were, however, more dead cells (stained by Evans blue) in the mesocarp of the fruit stored at 5°C. There was a more considerable increase in the electrolyte leakage rate in both fruit tissues held at 5°C than 25°C. The CI was correlated with malondialdehyde (MDA) levels in the tissues. The MDA of fruit exocarp at 5°C was 1.6 fold higher than that at 25°C on day 6, while the lipoxygenase (LOX) activity in mesocarp was 50% higher in fruit stored at a lower temperature. The action of ascorbate peroxidase (APX) was high in the exocarp of the fruit stored at 5°C, but there appeared to be a continuous depletion of the co-substrate or ascorbic acid. In conclusion, the CI in the exocarp was mainly associated with a high level of reactive oxygen species (ROS). In contrast, the CI in the mesocarp appeared to be primarily associated with increased lipid peroxidation by the elevated LOX activity under cold stress compared to storage at 25°C.

scholarly journals BA6 Induces Apoptosis via Stimulation of Reactive Oxygen Species and Inhibition of Oxidative Phosphorylation in Human Lung Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Meng-Hsuan Cheng ◽  
Hung-Ling Huang ◽  
Yen-You Lin ◽  
Kuan-Hao Tsui ◽  
Pei-Chin Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Oxygen Species ◽  
Apoptotic Pathway ◽  
Induced Apoptosis

Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in turn caused the loss of mitochondrial membrane potential (MMP). The increase of oxidative stress in lung cancer cells treated with BA6 was accompanied by a decrease in the expression of antioxidant enzymes Cu/Zn SOD, MnSOD, and catalase. In addition, OXPHOS performed in the mitochondria and glycolysis in the cytoplasm were inhibited, which subsequently reduced downstream ATP production. Pretreatment with mitochondria-targeted antioxidant MitoTEMPO reduced BA6-induced apoptosis through the mitochondria-dependent apoptotic pathway, which was accompanied by increased cell viability, decreased mtROS, enhanced MMP, and suppressed expression of cleaved caspase-3 and caspase-9 proteins. In conclusion, the results of this study clarify the mechanism of BA6-induced apoptosis in lung cancer cells via the mitochondrial apoptotic pathway, suggesting that it is a potentially innovative alternative to the treatment of human lung cancer.

scholarly journals Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 532 ◽  
Author(s):  
Juhyun Shin ◽  
Min-Ho Song ◽  
Jae-Wook Oh ◽  
Young-Soo Keum ◽  
Ramesh Kumar Saini
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Research Gaps ◽  
Cytotoxic Effects ◽  
Normal Cells ◽  
Anti Cancer ◽  
Antioxidant Function ◽  
High Level ◽  
Β Carotene

Carotenoids are well known for their potent antioxidant function in the cellular system. However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis. In recent years, the pro-oxidant function of several common dietary carotenoids, including astaxanthin, β-carotene, fucoxanthin, and lycopene, has been investigated for their effective killing effects on various cancer cell lines. Besides, when carotenoids are delivered with ROS-inducing cytotoxic drugs (e.g., anthracyclines), they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants. These dynamic actions of carotenoids can optimize oxidative stress in normal cells while enhancing oxidative stress in cancer cells. This review discusses possible mechanisms of carotenoid-triggered ROS production in cancer cells, the activation of pro-apoptotic signaling by ROS, and apoptotic cell death. Moreover, synergistic actions of carotenoids with ROS-inducing anti-cancer drugs are discussed, and research gaps are suggested.

scholarly journals Metformin Induces Apoptosis and Alters Cellular Responses to Oxidative Stress in Ht29 Colon Cancer Cells: Preliminary Findings

2018 ◽  
Vol 19 (5) ◽  
pp. 1478 ◽  
Author(s):  
Paola Sena ◽  
Stefano Mancini ◽  
Marta Benincasa ◽  
Francesco Mariani ◽  
Carla Palumbo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cellular Responses ◽  
Colon Cancer Cells

scholarly journals Protocatechuic Acid, a Simple Plant Secondary Metabolite, Induced Apoptosis by Promoting Oxidative Stress through HO-1 Downregulation and p21 Upregulation in Colon Cancer Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1485
Author(s):  
Rosaria Acquaviva ◽  
Barbara Tomasello ◽  
Claudia Di Giacomo ◽  
Rosa Santangelo ◽  
Alfonsina La Mantia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Reactive Oxygen Species ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Protocatechuic Acid ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Colon Cancer Cells ◽  
Glutamylcysteine Synthetase

Gastrointestinal cancers, particularly colorectal cancer, are mainly influenced by the dietary factor. A diet rich in fruits and vegetables can help to reduce the incidence of colorectal cancer thanks to the phenolic compounds, which possess antimutagenic and anticarcinogenic properties. Polyphenols, alongside their well-known antioxidant properties, also show a pro-oxidative potential, which makes it possible to sensitize tumor cells to oxidative stress. HO-1 combined with antioxidant activity, when overexpressed in cancer cells, is involved in tumor progression, and its inhibition is considered a feasible therapeutic strategy in cancer treatment. In this study, the effects of protocatechuic acid (PCA) on the viability of colon cancer cells (CaCo-2), annexin V, LDH release, reactive oxygen species levels, total thiol content, HO-1, γ-glutamylcysteine synthetase, and p21 expression were evaluated. PCA induced, in a dose-dependent manner, a significantly reduced cell viability of CaCo-2 by oxidative/antioxidant imbalance. The phenolic acid induced modifications in levels of HO-1, non-proteic thiol groups, γ-glutamylcysteine synthetase, reactive oxygen species, and p21. PCA induced a pro-oxidant effect in cancer cells, and the in vitro pro-apoptotic effect on CaCo-2 cells is mediated by the modulation of redox balance and the inhibition of the HO-1 system that led to the activation of p21. Our results suggest that PCA may represent a useful tool in prevention and/or therapy of colon cancer.

scholarly journals Sestrins as a Therapeutic Bridge between ROS and Autophagy in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1415 ◽  
Author(s):  
Sánchez-Álvarez ◽  
Strippoli ◽  
Donadelli ◽  
Bazhin ◽  
Cordani
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Personalized Medicine ◽  
Cancer Cells ◽  
Cell Metabolism ◽  
Tumor Therapy ◽  
Nutrient Sensing ◽  
Metabolic Adaptation ◽  
Pharmacological Intervention ◽  
Oxygen Species

: The regulation of Reactive Oxygen Species (ROS) levels and the contribution therein from networks regulating cell metabolism, such as autophagy and the mTOR-dependent nutrient-sensing pathway, constitute major targets for selective therapeutic intervention against several types of tumors, due to their extensive rewiring in cancer cells as compared to healthy cells. Here, we discuss the sestrin family of proteins—homeostatic transducers of oxidative stress, and drivers of antioxidant and metabolic adaptation—as emerging targets for pharmacological intervention. These adaptive regulators lie at the intersection of those two priority nodes of interest in antitumor intervention—ROS control and the regulation of cell metabolism and autophagy—therefore, they hold the potential not only for the development of completely novel compounds, but also for leveraging on synergistic strategies with current options for tumor therapy and classification/stadiation to achieve personalized medicine.

scholarly journals Reactive Oxygen Species, Metabolic Plasticity, and Drug Resistance in Cancer

2020 ◽  
Vol 21 (10) ◽  
pp. 3412 ◽  
Author(s):  
Vikas Bhardwaj ◽  
Jun He
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Tca Cycle ◽  
Metabolic Adaptation ◽  
Oxygen Species ◽  
Metabolic Plasticity ◽  
The Tca Cycle ◽  
Clinical Benefits ◽  
High Level

The metabolic abnormality observed in tumors is characterized by the dependence of cancer cells on glycolysis for their energy requirements. Cancer cells also exhibit a high level of reactive oxygen species (ROS), largely due to the alteration of cellular bioenergetics. A highly coordinated interplay between tumor energetics and ROS generates a powerful phenotype that provides the tumor cells with proliferative, antiapoptotic, and overall aggressive characteristics. In this review article, we summarize the literature on how ROS impacts energy metabolism by regulating key metabolic enzymes and how metabolic pathways e.g., glycolysis, PPP, and the TCA cycle reciprocally affect the generation and maintenance of ROS homeostasis. Lastly, we discuss how metabolic adaptation in cancer influences the tumor’s response to chemotherapeutic drugs. Though attempts of targeting tumor energetics have shown promising preclinical outcomes, the clinical benefits are yet to be fully achieved. A better understanding of the interaction between metabolic abnormalities and involvement of ROS under the chemo-induced stress will help develop new strategies and personalized approaches to improve the therapeutic efficiency in cancer patients.

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