Abstract
Cancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxygen species (ROS) can indeed play an important role in the initiation and progression of cancer, and advanced stage tumors frequently exhibit high basal levels of ROS that stimulate cell proliferation and promote genetic instability. In addition, an inverse correlation between histological grade and antioxidant enzyme activities is frequently observed in human tumors, further supporting the existence of a redox dysregulation in cancer cells. This biochemical property can be exploited by using redox-modulating compounds, which represent an interesting approach to induce cancer cell death. Thus, we have developed a new strategy based on the use of pharmacologic concentrations of ascorbate and redox-active quinones. Ascorbate-driven quinone redox cycling leads to ROS formation and provokes an oxidative stress that preferentially kills cancer cells and spares healthy tissues. Cancer cell death occurs through necrosis and the underlying mechanism implies an energetic impairment (ATP depletion) that is likely due to glycolysis inhibition. Additional mechanisms that participate to cell death include calcium equilibrium impairment and oxidative cleavage of protein chaperone Hsp90. Given the low systemic toxicity of ascorbate and the impairment of crucial survival pathways when associated with redox-active quinones, these combinations could represent an original approach that could be combined to standard cancer therapy.
Keywords: Ascorbate, cancer, quinone, redox cycling, oxidative stress, genetic instability, superoxide dismutase, glutathione (GSH), glucose transporters, ROS, NADPH-dependent selenoenzyme, ascorbate/menadione combination, asparaginase, intercalating agents, Ascorbate-driven quinone redox cycling leads
Anti-Cancer Agents in Medicinal Chemistry
Title: Redox-Active Quinones and Ascorbate: An Innovative Cancer Therapy That Exploits the Vulnerability of Cancer Cells to Oxidative Stress
Volume: 11 Issue: 2
Author(s): Julien Verrax, Raphael Beck, Nicolas Dejeans, Christophe Glorieux, Brice Sid, Rozangela C. Pedrosa, Julio Benites, David Vasquez, Jaime A. Valderrama and Pedro Buc Calderon
Affiliation:
Keywords: Ascorbate, cancer, quinone, redox cycling, oxidative stress, genetic instability, superoxide dismutase, glutathione (GSH), glucose transporters, ROS, NADPH-dependent selenoenzyme, ascorbate/menadione combination, asparaginase, intercalating agents, Ascorbate-driven quinone redox cycling leads
Abstract: Cancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxygen species (ROS) can indeed play an important role in the initiation and progression of cancer, and advanced stage tumors frequently exhibit high basal levels of ROS that stimulate cell proliferation and promote genetic instability. In addition, an inverse correlation between histological grade and antioxidant enzyme activities is frequently observed in human tumors, further supporting the existence of a redox dysregulation in cancer cells. This biochemical property can be exploited by using redox-modulating compounds, which represent an interesting approach to induce cancer cell death. Thus, we have developed a new strategy based on the use of pharmacologic concentrations of ascorbate and redox-active quinones. Ascorbate-driven quinone redox cycling leads to ROS formation and provokes an oxidative stress that preferentially kills cancer cells and spares healthy tissues. Cancer cell death occurs through necrosis and the underlying mechanism implies an energetic impairment (ATP depletion) that is likely due to glycolysis inhibition. Additional mechanisms that participate to cell death include calcium equilibrium impairment and oxidative cleavage of protein chaperone Hsp90. Given the low systemic toxicity of ascorbate and the impairment of crucial survival pathways when associated with redox-active quinones, these combinations could represent an original approach that could be combined to standard cancer therapy.
Export Options
About this article
Cite this article as:
Verrax Julien, Beck Raphael, Dejeans Nicolas, Glorieux Christophe, Sid Brice, C. Pedrosa Rozangela, Benites Julio, Vasquez David, A. Valderrama Jaime and Buc Calderon Pedro, Redox-Active Quinones and Ascorbate: An Innovative Cancer Therapy That Exploits the Vulnerability of Cancer Cells to Oxidative Stress, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (2) . https://dx.doi.org/10.2174/187152011795255902
DOI https://dx.doi.org/10.2174/187152011795255902 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
Related Articles
-
Common Themes in RNA Subcellular Transport, Stress Granule Formation and Abnormal Protein Aggregation
Current Chemical Biology Membrane Receptor and Antiangiogenic Targeted Therapies in the Treatment of Cancer
Current Cancer Therapy Reviews Synthesis of 2,5-Disubstituted-1,3,4-oxadiazole Analogs as Novel Anticancer and Antimicrobial Agents
Letters in Drug Design & Discovery Interferon-Alpha in the Treatment of Philadelphia-Negative Chronic Myeloproliferative Neoplasms. Status and Perspectives
Current Drug Targets Resveratrol: A Natural Polyphenol with Multiple Chemopreventive Properties (Review)
Current Drug Metabolism Factors Promoting Tamoxifen Resistance in Breast Cancer via Stimulating Breast Cancer Stem Cell Expansion
Current Medicinal Chemistry Flavonoid Antioxidants
Current Medicinal Chemistry Topical Dermatological Drug Delivery: Quo Vadis?
Current Drug Delivery Preventive and Therapeutic Effects of the Retinoid X Receptor Agonist Bexarotene on Tumors
Current Drug Metabolism Revision of the Regioselectivity of the Beirut Reaction of Monosubstituted Benzofuroxans with Benzoylacetonitrile. 6-Substituted quinoxaline-2-carbonitrile 1,4- dioxides: Structural Characterization and Estimation of Anticancer Activity and Hypoxia Selectivity
Current Organic Synthesis Gold Nanoparticle-Lignan Complexes Inhibited MCF-7 Cell Proliferation in vitro: A Novel Conjugation for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Rational Targeting of Peroxisome Proliferating Activated Receptor Subtypes
Current Medicinal Chemistry Orthotopic Liver Transplantation in Non-Alcoholic Fatty Liver Disease Patients
Reviews on Recent Clinical Trials Preface:
Clinical Cancer Drugs Endometriosis and Gynecological Cancer
Current Women`s Health Reviews Metastasis-Initiating Cells in Renal Cancer
Current Signal Transduction Therapy Interactome Analysis of the Differentially Expressed Proteins in Uterine Leiomyoma
Anti-Cancer Agents in Medicinal Chemistry The Synthesis and Use of Boronated Amino Acids for Boron Neutron Capture Therapy
Anti-Cancer Agents in Medicinal Chemistry Use of Positron Emission Tomography for Target Volume Definition
Current Radiopharmaceuticals Immunosuppressive and Antiviral Treatment of Inflammatory Cardiomyopathy
Recent Patents on Cardiovascular Drug Discovery