Targeting oxidative stress in disease: promise and limitations of antioxidant therapy

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(9), P. 689 - 709

Published: June 30, 2021

Language: Английский

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Oxidative Stress in Cancer

Cancer Cell, Journal Year: 2020, Volume and Issue: 38(2), P. 167 - 197

Published: July 9, 2020

Language: Английский

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Role of Glutathione in Cancer: From Mechanisms to Therapies

Biomolecules, Journal Year: 2020, Volume and Issue: 10(10), P. 1429 - 1429

Published: Oct. 9, 2020

Glutathione (GSH) is the most abundant non-protein thiol present at millimolar concentrations in mammalian tissues. As an important intracellular antioxidant, it acts as a regulator of cellular redox state protecting cells from damage caused by lipid peroxides, reactive oxygen and nitrogen species, xenobiotics. Recent studies have highlighted importance GSH key signal transduction reactions controller cell differentiation, proliferation, apoptosis, ferroptosis immune function. Molecular changes antioxidant system disturbances homeostasis been implicated tumor initiation, progression, treatment response. Hence, has both protective pathogenic roles. Although healthy crucial for removal detoxification carcinogens, elevated levels are associated with progression increased resistance to chemotherapeutic drugs. Recently, several novel therapies developed target tumors means response decreased drug resistance. In this comprehensive review we explore mechanisms functionalities different therapeutic approaches that either directly, indirectly or use GSH-based prodrugs. Consideration also given computational methods used describe related processes silico testing effects.

Language: Английский

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The double-edged roles of ROS in cancer prevention and therapy

Theranostics, Journal Year: 2021, Volume and Issue: 11(10), P. 4839 - 4857

Published: Jan. 1, 2021

Reactive oxygen species (ROS) serve as cell signaling molecules generated in oxidative metabolism and are associated with a number of human diseases. The reprogramming redox induces abnormal accumulation ROS cancer cells. It has been widely accepted that play opposite roles tumor growth, metastasis apoptosis according to their different distributions, concentrations durations specific subcellular structures. These double-edged progression include the ROS-dependent malignant transformation stress-induced death. In this review, we summarize notable literatures on generation scavenging, discuss related signal transduction networks corresponding anticancer therapies. There is no doubt an improved understanding sophisticated mechanism biology imperative conquer cancer.

Language: Английский

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ROS systems are a new integrated network for sensing homeostasis and alarming stresses in organelle metabolic processes

Redox Biology, Journal Year: 2020, Volume and Issue: 37, P. 101696 - 101696

Published: Aug. 27, 2020

Reactive oxygen species (ROS) are critical for the progression of cardiovascular diseases, inflammations and tumors. However, mechanisms how ROS sense metabolic stress, regulate pathways initiate proliferation, inflammation cell death responses remain poorly characterized. In this analytic review, we concluded that: 1) Based on different features functions, eleven types can be classified into seven functional groups: stress-sensing, chemical connecting, organelle communication, stress branch-out, inflammasome-activating, dual functions triple ROS. 2) Among generation systems, mitochondria consume most amount oxygen; nine generated; thus, mitochondrial systems serve as central hub connecting with inflammasome activation, trained immunity immunometabolic pathways. 3) Increased nuclear production significantly promotes in comparison to that other organelles. Nuclear a convergent decision-makers connect unbearable alarming stresses death. 4) Balanced levels indicate physiological homeostasis various processes subcellular organelles cytosol, while imbalanced present alarms pathological processes. these analyses, propose working model new integrated network sensing Our provides novel insights roles bridging inflammation, tumorigenesis; provide therapeutic targets treating those diseases. (Word count: 246).

Language: Английский

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Targeting mitochondrial metabolism for precision medicine in cancer

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(7), P. 1304 - 1317

Published: July 1, 2022

Abstract During decades, the research field of cancer metabolism was based on Warburg effect, described almost one century ago. Lately, key role mitochondria in development has been demonstrated. Many mitochondrial pathways including oxidative phosphorylation, fatty acid, glutamine, and carbon are altered tumors, due to mutations oncogenes tumor suppressor genes, as well metabolic enzymes. This results reprogramming that sustains rapid cell proliferation can lead an increase reactive oxygen species used by cells maintain pro-tumorigenic signaling while avoiding cellular death. The knowledge acquired importance is now being translated into clinical practice. Detailed genomic, transcriptomic, metabolomic analysis tumors necessary develop more precise treatments. successful use drugs targeting enzymes highlighted potential for their precision medicine many therapeutic candidates trials. However, efficient personalized proved challenging combination with other strategies such chemocytotoxic drugs, immunotherapy, ketogenic or calorie restriction diets likely boost potential. In this review, we summarize main features, pathways, alterations different types. We also present overview current inhibitors, highlight attractive targets, discuss challenges translation these approaches indisputable presents several targets both tailored therapy.

Language: Английский

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Antioxidant Therapy in Cancer: Rationale and Progress

Antioxidants, Journal Year: 2022, Volume and Issue: 11(6), P. 1128 - 1128

Published: June 8, 2022

Cancer is characterized by increased oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants. Enhanced ROS accumulation, as a result of metabolic disturbances signaling aberrations, can promote carcinogenesis malignant progression inducing gene mutations activating pro-oncogenic signaling, providing possible rationale for targeting stress in cancer treatment. While numerous antioxidants have demonstrated therapeutic potential, their clinical efficacy remains unproven. Here, we review the for, recent advances in, pre-clinical research on antioxidant therapy cancer, including with nonenzymatic antioxidants, such NRF2 activators, vitamins, N-acetylcysteine GSH esters, or enzymatic NOX inhibitors SOD mimics. In addition, will offer insights into prospective options improving effectiveness therapy, which may expand its applications

Language: Английский

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NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(17), P. 11632 - 11655

Published: Aug. 31, 2023

NADPH oxidases (NOXs) form a family of electron-transporting membrane enzymes whose main function is reactive oxygen species (ROS) generation. Strong evidence suggests that ROS produced by NOX are major contributors to oxidative damage under pathologic conditions. Therefore, blocking the undesirable actions these therapeutic strategy for treating various pathological disorders, such as cardiovascular diseases, inflammation, and cancer. To date, identification selective inhibitors quite challenging, precluding pharmacologic demonstration targets in vivo. The aim this Perspective furnish an updated outlook about small-molecule described over last two decades. Structures, activities, vitro/in vivo specificity discussed, well biological assays used.

Language: Английский

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Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(18)

Published: Jan. 15, 2024

Abstract Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad vital functions across diverse cellular processes. Dysfunctions within mitochondria serve catalysts for various diseases, prompting widespread demise. Mounting research on remedying damaged indicates that constitute valuable target therapeutic intervention against diseases. But less clinical practice and lower recovery rate imply limitation traditional drugs, which need further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution high efficacy by capitalizing excellent nanomaterials targeting drug delivery. Mitochondria‐remedying nanodrugs achieved ideal effects. This review elucidates significance in cells organs, while also compiling mortality data related Correspondingly, nanodrug‐mediate strategies applicable mitochondria‐remedying disease are detailed, with full understanding roles dysfunction advantages nanodrugs. In addition, future challenges directions discussed. conclusion, this provides comprehensive insights into design development nanodrugs, aiming to help scientists who desire extend their fields engage interdisciplinary subject.

Language: Английский

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Nanomaterials‐Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(16)

Published: Feb. 21, 2024

Abstract Cancer cells typically display redox imbalance compared with normal due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This may regulate gene expression, alter protein stability, modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra‐ or extracellular states of cancer at varying state progression trigger programmed death if exceeded a certain threshold, enabling therapeutic selectivity overcoming resistance radiotherapy chemotherapy. Nanotechnology provides new opportunities for modulating their excellent designability high reactivity. Various nanomaterials are widely researched enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, both. Here, physiological features described challenges illustrated. Then, that classified elaborated upon based on ability target regulations. Finally, future perspectives this field proposed. It is hoped review guidance design nanomaterials‐based approaches involving therapy, especially cancers resistant chemotherapy, etc.

Language: Английский

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