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
-
Risperidone: A Commentary on Drug Profiling
Current Drug Discovery Technologies Toxic Effects of Aflatoxin B1 on Embryonic Development of Zebrafish (Danio rerio): Potential Activity of Piceatannol Encapsulated Chitosan/poly (Lactic Acid) Nanoparticles
Anti-Cancer Agents in Medicinal Chemistry Beneficial and Adverse Effects of Molecularly Targeted Therapies for Acute Promyelocytic Leukemia in Central Nervous System
CNS & Neurological Disorders - Drug Targets Nanotechnology: A New Paradigm in Cosmeceuticals
Recent Patents on Drug Delivery & Formulation Editorial [Hot topic: Role of Apoptosis in Chemotherapy (Guest Editors: George G. Chen and Paul B.S. Lai)]
Current Drug Targets Metabotropic Glutamate Receptors in Central Nervous System Diseases
Current Drug Targets Patents in Nanobiotechnology: A Cross Jurisdictional Approach
Recent Patents on Biotechnology New Developments and Prospective Applications for β (1,3) Glucans
Recent Patents on Biotechnology Targeting Translation for Treatment of Cancer - A Novel Role for IRES?
Current Cancer Drug Targets Can Breast Cancer Stem Cells Evade the Immune System?
Current Medicinal Chemistry Targeted Radiotherapy for Malignant Gliomas
Current Drug Discovery Technologies Tumoral Drug Metabolism: Perspectives and Therapeutic Implications
Current Drug Metabolism Titanium Tetrachloride-mediated Synthesis of Diarylmethanes through the Reaction of Benzyl Alcohol Derivatives with Aromatic Substrates
Current Organic Chemistry The Adenine Nucleotide Translocator: A New Potential Chemotherapeutic Target
Current Drug Targets Cardiotoxicity of Tyrosine-Kinase-Targeting Drugs
Cardiovascular & Hematological Agents in Medicinal Chemistry Developmental Immunotoxicity (DIT) in Drug Safety Testing: Matching DIT Testing to Adverse Outcomes and Childhood Disease Risk
Current Drug Safety Synthesis, Anticancer, and Antibacterial Activity of Betulinic and Betulonic Acid C-28-Triphenylphosphonium Conjugates with Variable Alkyl Linker Length
Anti-Cancer Agents in Medicinal Chemistry The Association of Very High Hair Manganese Accumulation and High Oxidative Stress in Mongolian People
Current Aging Science “Non-Taxifolin” Derived Flavonolignans: Phytochemistry and Biology
Current Pharmaceutical Design Serum Proteomic Analysis of the Patients Suffering with End Stage Renal Disease and Left Ventricular Hypertrophy
Current Biomarkers (Discontinued)