Abstract:
:Redox dysregulation originating from metabolic alterations and dependence on mitogenic and survival signaling through reactive oxygen species represents a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics. This review will present an update on drug discovery, target identification, and mechanisms of action of experimental redox chemotherapeutics with a focus on pro- and antioxidant redox modulators now in advanced phases of preclinal and clinical development. Recent research indicates that numerous oncogenes and tumor suppressor genes exert their functions in part through redox mechanisms amenable to pharmacological intervention by redox chemotherapeutics. The pleiotropic action of many redox chemotherapeutics that involves simultaneous modulation of multiple redox sensitive targets can overcome cancer cell drug resistance originating from redundancy of oncogenic signaling and rapid mutation.Moreover, some redox chemotherapeutics may function according to the concept of synthetic lethality (i.e., drug cytotoxicity is confined to cancer cells that display loss of function mutations in tumor suppressor genes or upregulation of oncogene expression). The impressive number of ongoing clinical trials that examine therapeutic performance of novel redox drugs in cancer patients demonstrates that redox chemotherapy has made the crucial transition from bench to bedside.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Wondrak GTdoi
10.1089/ars.2009.2541subject
Has Abstractpub_date
2009-12-01 00:00:00pages
3013-69issue
12eissn
1523-0864issn
1557-7716journal_volume
11pub_type
杂志文章,评审abstract:SIGNIFICANCE:Heart disease is the primary cause of death in the industrialized world. Cardiac failure is dictated by an uncompensated reduction in the number of viable and fully functional cardiomyocytes. While current pharmacological therapies alleviate the symptoms associated with cardiac deterioration, heart transpl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.5875
更新日期:2014-11-10 00:00:00
abstract::Hydrogen sulfide (H(2)S) is a gasotransmitter with multifaceted physiological functions, including the regulation of glucose metabolism. Methylglyoxal (MG) is an intermediate of glucose metabolism and plays an important role in the pathogenesis of insulin resistance syndromes. In the present study, we investigated the...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2918
更新日期:2010-05-01 00:00:00
abstract::Transforming growth factor-betas (TGF-beta) regulate a wide variety of cellular functions in normal development and are involved in both tissue homeostasis and disease pathogenesis. The regulation of the TGF-beta family of growth factors is unique because they are targeted to the extracellular matrix in a biologically...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1914
更新日期:2008-02-01 00:00:00
abstract::Homocysteine is a thiol-containing amino acid that has gained notoriety because its elevation in the plasma is correlated with complex and multifactorial diseases, including cardiovascular diseases, neurodegenerative diseases, and neural tube defects. Homocysteine is redox-active, and its toxic effects have been frequ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.547
更新日期:2005-05-01 00:00:00
abstract:UNLABELLED:In living systems, the mechanisms of inheritance involving gene expression are operated by (i) the traditional model of genetics where the deoxyribonucleic acid (DNA) transcription and messenger ribonucleic acid stability are influenced by the DNA sequences and any aberrations in the primary DNA sequences an...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4600
更新日期:2012-07-15 00:00:00
abstract::Loss of redox homeostasis and formation of excessive free radicals play an important role in the pathogenesis of kidney disease and hypertension. Free radicals such as reactive oxygen species (ROS) are necessary in physiologic processes. However, loss of redox homeostasis contributes to proinflammatory and profibrotic...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2008.2034
更新日期:2008-12-01 00:00:00
abstract::Alteration in neurotrophic factors support and antioxidant defenses in the central nervous system (CNS) along with deficit of ferritin have been associated with idiopathic Parkinson's disease (PD). The objectives were to analyze in the cerebrospinal fluid (CSF) of patients with PD and controls the following: (i) the l...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6423
更新日期:2015-10-10 00:00:00
abstract:AIMS:Monothiol glutaredoxins (1-C-Grxs) are small proteins linked to the cellular iron and redox metabolism. Trypanosoma brucei brucei, model organism for human African trypanosomiasis, expresses three 1-C-Grxs. 1-C-Grx1 is a highly abundant mitochondrial protein capable to bind an iron-sulfur cluster (ISC) in vitro us...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4859
更新日期:2013-09-01 00:00:00
abstract:: Significance: Since the discovery of vascular stem cells, there has been considerable advancement in comprehending the nature and functions of these cells. Due to their differentiation potential to repair endothelial cells and to participate in lesion formation during vasc...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8199
更新日期:2021-01-19 00:00:00
abstract::Peroxiredoxins (Prxs) are a family of peroxidases that reduce peroxides, with a conserved cysteine residue (the peroxidatic Cys) serving as the site of oxidation by peroxides. Peroxides oxidize the peroxidatic Cys-SH to Cys-SOH, which then reacts with another cysteine residue (typically the resolving Cys [C(R)]) to fo...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3393
更新日期:2011-08-01 00:00:00
abstract::Exposure of neonatal rat cardiac myocytes to palmitate and glucose produces apoptosis as seen by cytochrome c release, caspase 3-like activation, DNA laddering, and poly(ADP-ribose) polymerase cleavage. The purpose of this study was to understand the role of reactive oxygen species in the initiation of programmed cell...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308601750100524
更新日期:2001-02-01 00:00:00
abstract:SIGNIFICANCE:Dysregulation of cortical and striatal neuronal processing plays a critical role in Huntington's disease (HD), a dominantly inherited condition that includes a progressive deterioration of cognitive and motor control. Growing evidence indicates that ascorbate (AA), an antioxidant vitamin, is released into ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5387
更新日期:2013-12-10 00:00:00
abstract::To test the hypothesis that the inducible nitric oxide synthase (iNOS) is involved in mediating the toll-like receptor 4-dependent effects on the liver in the onset of fructose-induced steatosis, wild-type and iNOS knockout (iNOS(-/-)) mice were either fed tap water or 30% fructose solution for 8 weeks. Chronic consum...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3263
更新日期:2011-06-01 00:00:00
abstract::Neurons are extremely active cells and metabolize up to 20% of the oxygen that was consumed by the organism. Despite their highly oxygenic metabolism, neuronal cells have a lower capacity to neutralize the reactive oxygen species (ROS) that they generate or to which they are exposed. High levels of ROS can lead to acc...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.9.211
更新日期:2007-02-01 00:00:00
abstract:AIMS:Macrophages are of key importance for tissue repair after myocardial infarction (MI). Hydrogen sulfide (H2S) has been shown to exert cardioprotective effects in MI. However, the mechanisms by which H2S modulates cardiac remodeling and repair post-MI remain to be clarified. RESULTS:In our current study, we showed ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6577
更新日期:2016-08-10 00:00:00
abstract::Secretory and transmembrane proteins are correctly folded or processed in the endoplasmic reticulum (ER). Various stresses disturb ER function and provoke the accumulation of unfolded proteins in the ER lumen. This condition is termed ER stress. Recently, ER stress has been linked to neuronal death in various neurodeg...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.1520
更新日期:2007-05-01 00:00:00
abstract::Epithelial to mesenchymal transition (EMT) is a fundamental process, paradigmatic of the concept of cell plasticity, that leads epithelial cells to lose their polarization and specialized junctional structures, to undergo cytoskeleton reorganization, and to acquire morphological and functional features of mesenchymal-...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.2737
更新日期:2010-06-15 00:00:00
abstract::Vitamin K epoxide, a by-product of the carboxylation of blood coagulation factors, is reduced to vitamin K by an enzymatic system possessing vitamin K epoxide reductase (VKOR) activity. This system is the target of coumarin-derived drugs widely used in thrombosis therapy and prophylaxis. Recently, the key protein of t...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.347
更新日期:2006-03-01 00:00:00
abstract:SIGNIFICANCE:In bacteria, transcriptional responses to reactive oxygen and nitrogen species (ROS and RNS, respectively) are typically coordinated by regulatory proteins that employ metal centers or reactive thiols to detect the presence of those species. This review is focused on the structure, function and mechanism o...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4533
更新日期:2012-11-01 00:00:00
abstract:SIGNIFICANCE:Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4, and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms. They play an important role in the adjustment of metabolic pathways in alterations of the nutritional status. Recent Advances: Recent studies...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7270
更新日期:2018-03-10 00:00:00
abstract:: Aims: To ascertain if human pericytes produce SPARC (acronym for Secreted Protein Acidic and Cysteine Rich), a matricellular protein implicated in the regulation of cell proliferation, migration, and cell-matrix interactions; clarify if SPARC expression in cardiac pericyte...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7969
更新日期:2020-11-23 00:00:00
abstract::Increased free radical generation and decreased efficiency of the reparative/degradative mechanisms both primarily contribute to age-related elevation in the level of oxidative stress and brain damage. Excess formation of reactive oxygen and nitrogen species can cause proteasomal dysfunction and protein overloading. T...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.444
更新日期:2006-03-01 00:00:00
abstract:AIMS:Pulmonary infections with Pseudomonas aeruginosa are a serious clinical problem and are often lethal. Because many strains of P. aeruginosa are resistant to antibiotics, therapeutic options are limited. Neutrophils play an important role in the host's early acute defense against pulmonary P. aeruginosa. Therefore,...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2014.5979
更新日期:2015-05-01 00:00:00
abstract::In the brain, the mu-opioid receptor (MOR) activates neural nitric oxide synthase (nNOS) through the PI3K/Akt pathway. The resulting nitric oxide (NO) enhances the function of the glutamate N-methyl-d-aspartate receptor (NMDAR)/calcium and calmodulin-dependent serine/threonine kinase (CaMKII), which subsequently dimin...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3511
更新日期:2011-06-15 00:00:00
abstract::Previous reports have shown that the human immunodeficiency virus (HIV) regulatory protein Tat has both pro-oxidant and pro-inflammatory properties, suggesting that Tat might contribute to the neurological complications of HIV. However, the intracellular mechanisms whereby Tat triggers free radical production and infl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2097
更新日期:2009-02-01 00:00:00
abstract::Physiological levels of reactive oxygen species (ROS) play an important regulatory role through various signaling transduction pathways in folliculogenesis, oocyte maturation, endometrial cycle, luteolysis, implantation, embryogenesis, and pregnancy. Persistent and elevated generation of ROS leads to a disturbance of ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1964
更新日期:2008-08-01 00:00:00
abstract::Fluid shear stress plays a critical role in the regulation of vascular biology and its pathology, such as atherosclerosis, via modulation of redox balance. Both pro-atherogenic (either oscillatory or turbulent, nonunidirectional) shear stress and anti-atherogenic (either steady or pulsatile, unidirectional laminar) sh...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3433
更新日期:2011-09-01 00:00:00
abstract::This brief review first touches on the origins of the earth's oxygen. It then identifies and locates the principal oxygen sensor in vertebrates, the carotid body (CB). The CB is unique in that in human subjects, it is the only sensor of lower than normal levels in the partial pressure of oxygen (hypoxia, HH). Another ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1546
更新日期:2007-06-01 00:00:00
abstract::This work rests on our previous report (J Cereb Blood Flow Metab 30: 1275-1287, 2010) recognizing that glutamate (Glu) oxaloacetate transaminase (GOT) is induced when brain tissue hypoxia is corrected during acute ischemic stroke (AIS). GOT can metabolize Glu into tricarboxylic acid cycle intermediates and may therefo...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.3930
更新日期:2011-05-15 00:00:00
abstract::Reactive oxygen species (ROS) have multifaceted roles in the orchestration of plant gene expression and gene-product regulation. Cellular redox homeostasis is considered to be an "integrator" of information from metabolism and the environment controlling plant growth and acclimation responses, as well as cell suicide ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2008.2177
更新日期:2009-04-01 00:00:00