Abstract
Control of redox homeostasis is crucial for a number of cellular processes with deregulation leading to a number of serious consequences including oxidative damage such induction of DNA base lesions. The DNA lesions caused by oxidative damage are principally repaired by the base excision repair (BER) pathway. Pharmacological inhibition of BER is becoming an increasingly active area of research with the emergence of PARP inhibitors in cancer therapy. The redox status of the cell is modulated by a number of systems, including a large number of anti-oxidant enzymes who function in the control of superoxide and hydrogen peroxide, and ultimately in the release of the damaging hydroxyl radical. Here we provide an overview of reactive oxygen species (ROS) production and its modulation by antioxidant enzymes. The review also discusses the effect of ROS on the BER pathway, particularly in relation to cancer. Finally, as the modulation of the redox environment is of interest in cancer therapy, with certain agents having the potential to reverse chemo- and radiotherapy resistance or treat therapy related toxicity, we discuss redox modulating agents currently under development.
Keywords: Base excision repair, cancer, homeostasis, redox
Current Molecular Pharmacology
Title: Base Excision Repair, the Redox Environment and Therapeutic Implications
Volume: 5
Author(s): S. J. Storr, C. M. Woolston and S. G. Martin
Affiliation:
Keywords: Base excision repair, cancer, homeostasis, redox
Abstract: Control of redox homeostasis is crucial for a number of cellular processes with deregulation leading to a number of serious consequences including oxidative damage such induction of DNA base lesions. The DNA lesions caused by oxidative damage are principally repaired by the base excision repair (BER) pathway. Pharmacological inhibition of BER is becoming an increasingly active area of research with the emergence of PARP inhibitors in cancer therapy. The redox status of the cell is modulated by a number of systems, including a large number of anti-oxidant enzymes who function in the control of superoxide and hydrogen peroxide, and ultimately in the release of the damaging hydroxyl radical. Here we provide an overview of reactive oxygen species (ROS) production and its modulation by antioxidant enzymes. The review also discusses the effect of ROS on the BER pathway, particularly in relation to cancer. Finally, as the modulation of the redox environment is of interest in cancer therapy, with certain agents having the potential to reverse chemo- and radiotherapy resistance or treat therapy related toxicity, we discuss redox modulating agents currently under development.
Export Options
About this article
Cite this article as:
J. Storr S., M. Woolston C. and G. Martin S., Base Excision Repair, the Redox Environment and Therapeutic Implications, Current Molecular Pharmacology 2012; 5 (1) . https://dx.doi.org/10.2174/1874467211205010088
DOI https://dx.doi.org/10.2174/1874467211205010088 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
- 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
-
Endothelial Dysfunction and the Effects of TNF Inhibitors on the Endothelium in Psoriasis and Psoriatic Arthritis: A Systematic Review
Current Pharmaceutical Design Current Perspectives of Healthy Mitochondrial Function for Healthy Neurons
Current Drug Targets Melatonin: Pharmacology, Functions and Therapeutic Benefits
Current Neuropharmacology An Agathokakological Tale of Δ<sup>9</sup>-THC: Exploration of Possible Biological Targets
Current Drug Targets Antiproliferative Activity of Olive Oil Phenolics against Human Melan oma Cells
Letters in Drug Design & Discovery GLP - 1 Analogs: Newer Molecules, Newer Uses
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Cardiac Effects of Anabolic Steroids: Hypertrophy, Ischemia and Electrical Remodelling as Potential Triggers of Sudden Death
Mini-Reviews in Medicinal Chemistry Disulfiram: An Old Therapeutic with New Applications
CNS & Neurological Disorders - Drug Targets Inhibition of Sphingomyelin Hydrolysis: Targeting the Lipid Mediator Ceramide as a Key Regulator of Cellular Fate
Current Medicinal Chemistry Versatility of Cancer Associated Fibroblasts: Commendable Targets for Anti-tumor Therapy
Current Drug Targets Beyond Ejection Fraction: Novel Clinical Approaches Towards Sudden Cardiac Death Risk Stratification in Patients with Dilated Cardiomyopathy
Current Cardiology Reviews Current Biology of MTP: Implications for Selective Inhibition
Current Topics in Medicinal Chemistry Cardiovascular Proteomics
Current Proteomics Omega-3 Fatty Acids and their Role in Central Nervous System - A Review
Current Medicinal Chemistry Urocortins: Putative Role in Cardiovascular Disease
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Central Blood Pressure and End-organ Damage
Current Hypertension Reviews Role of AMPK in Diabetic Cardiovascular Complications: An Overview
Cardiovascular & Hematological Disorders-Drug Targets Bayes Syndrome and Imaging Techniques
Current Cardiology Reviews Therapeutic Angiogenesis using Hepatocyte Growth Factor (HGF)
Current Gene Therapy Natural Product-Derived Small Molecule Activators of Hypoxia-Inducible Factor-1 (HIF-1)
Current Pharmaceutical Design