Abstract
Reactive oxygen species (ROS) play a central role as second messengers in many signal transduction pathways, where they can post-translationally modify proteins via the oxidation of redox sensitive cysteine residues. The range of cellular processes under redox regulation is extensive and includes both the proliferative and apoptotic pathways. Control of the cellular redox environment is therefore essential for normal physiological function and perturbations to this redox balance are characteristic of many pathological states. Oxidative stress is particularly prevalent in cancer, where many malignant cell types posses an abnormal redox metabolism involving down-regulation of antioxidant enzymes and impaired mitochondrial function. This provides a major opportunity to design therapeutic strategies to selectively target cancer cells based on their redox profile. This review will provide a background to this emerging field by summarizing the known redox biochemistry of ROS signaling. The mechanisms of ROS generation by the action of oxidoreductases and nitric oxide synthases will be discussed in conjunction with the cells major antioxidant defenses, with especial emphasis placed on the subcellular location of these redox reactions. The effect of ROS on proliferation and apoptosis will be examined by looking at interactions with transcription factors and the Akt, TNF and MAPK signaling pathways. The review will also outline the major differences in redox metabolism between cancer cells and their non-malignant counterparts. Although the full extent of the ROS regulation of signaling pathways is only beginning to be mapped, early indications are that this paradigm will provide new therapeutic targets for cancer therapy.
Keywords: ROS, thiol, signal, transduction, antioxidant, cysteine, cancer
Current Pharmaceutical Design
Title: The Redox Regulation of Thiol Dependent Signaling Pathways in Cancer
Volume: 12 Issue: 34
Author(s): Gregory I. Giles
Affiliation:
Keywords: ROS, thiol, signal, transduction, antioxidant, cysteine, cancer
Abstract: Reactive oxygen species (ROS) play a central role as second messengers in many signal transduction pathways, where they can post-translationally modify proteins via the oxidation of redox sensitive cysteine residues. The range of cellular processes under redox regulation is extensive and includes both the proliferative and apoptotic pathways. Control of the cellular redox environment is therefore essential for normal physiological function and perturbations to this redox balance are characteristic of many pathological states. Oxidative stress is particularly prevalent in cancer, where many malignant cell types posses an abnormal redox metabolism involving down-regulation of antioxidant enzymes and impaired mitochondrial function. This provides a major opportunity to design therapeutic strategies to selectively target cancer cells based on their redox profile. This review will provide a background to this emerging field by summarizing the known redox biochemistry of ROS signaling. The mechanisms of ROS generation by the action of oxidoreductases and nitric oxide synthases will be discussed in conjunction with the cells major antioxidant defenses, with especial emphasis placed on the subcellular location of these redox reactions. The effect of ROS on proliferation and apoptosis will be examined by looking at interactions with transcription factors and the Akt, TNF and MAPK signaling pathways. The review will also outline the major differences in redox metabolism between cancer cells and their non-malignant counterparts. Although the full extent of the ROS regulation of signaling pathways is only beginning to be mapped, early indications are that this paradigm will provide new therapeutic targets for cancer therapy.
Export Options
About this article
Cite this article as:
Giles I. Gregory, The Redox Regulation of Thiol Dependent Signaling Pathways in Cancer, Current Pharmaceutical Design 2006; 12 (34) . https://dx.doi.org/10.2174/138161206779010549
DOI https://dx.doi.org/10.2174/138161206779010549 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Insulin- and Growth Factor-Resistance Impairs Vascular Regeneration in Diabetes Mellitus
Current Vascular Pharmacology Inflammasome as a New Therapeutic Target for Diabetic Complications
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Endothelins and the Role of Endothelin Antagonists in the Management of Posttraumatic Vasospasm
Current Pharmaceutical Design The Immunosuppressive Role of Adenosine A2A Receptors in Ischemia Reperfusion Injury and Islet Transplantation
Current Diabetes Reviews Structure-Function Relationships of PEDF
Current Molecular Medicine Application of Carbon Nanotubes In Drug Delivery of Non-cancerous Diseases: A Review
Current Pharmaceutical Design Use of Telemetry Blood Pressure Transmitters to Measure Intracranial Pressure (ICP) in Freely Moving Rats
Current Neurovascular Research Non-Cardiomyocytes in Heart Regeneration
Current Drug Targets Fructose 1,6-Bisphosphate: A Summary of Its Cytoprotective Mechanism
Current Medicinal Chemistry A synopsis on the linkage between age-related dementias and vascular disorders
CNS & Neurological Disorders - Drug Targets Editorial [Hot Topic: Targeting the IGF-I Receptor Signaling Pathway:Implications for Human Cancer Therapy (Executive Editors: A. Ciampolillo and F. Giorgino) ]
Current Pharmaceutical Design Plasminogen Activation-Based Thrombolysis for Ischaemic Stroke: The Diversity of Targets may Demand New Approaches
Current Drug Targets Equol is Neuroprotective During Focal Cerebral Ischemia and Reperfusion that Involves p-Src and gp91<sup>phox</sup>
Current Neurovascular Research Carotid Endarterectomy and Carotid Artery Stenting Lead to Improved Cognitive Performance in Patients with Severe Carotid Artery Stenosis
Current Neurovascular Research Why and how do Microbubbles Enhance the Effectiveness of Diagnostic and Therapeutic Interventions in Cerebrovascular Disease?
Current Pharmaceutical Design Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair
Current Pharmaceutical Design Expression and Function of the Leukocyte Integrins in Medicine
Current Genomics Pharmacological Targeting of Neuronal Kv7.2/3 Channels: A Focus on Chemotypes and Receptor Sites
Current Medicinal Chemistry Advances in Characterization of Neuroprotective Peptide, Humanin
Current Medicinal Chemistry Therapeutic Use of Snake Venom Components: A Voyage from Ancient to Modern India
Mini-Reviews in Organic Chemistry