Abstract
Cancer cells show an up-regulation of glycolysis, they readily take up vitamin C, and they appear more susceptible to an oxidative stress than the surrounding normal cells. Here we compare, analyse and discuss these particular hallmarks by performing experiments in murine hepatomas (TLT cells) and freshly isolated mouse hepatocytes. The results show that rates of lactate formation are higher in TLT cells as compared to mouse hepatocytes, but their ATP content represents less than 25% of that in normal cells. The uptake of vitamin C is more important in hepatoma cells as compared to normal hepatocytes. This uptake mainly occurs through GLUT1 transporters. Hepatoma cells have less than 10% of antioxidant enzyme activities as compared to normal hepatocytes. This decrease includes not only the major antioxidant enzymes, namely catalase, superoxide dismutase and glutathione peroxidase, but also the GSH content. Moreover, catalase is almost not expressed in hepatoma cells as shown by western blot analysis. We explored therefore a selective exposure of cancer cells to an oxidative stress induced by pro-oxidant mixtures containing pharmacological doses of vitamin C and a redox active compound such as menadione (vitamin K3). Indeed, the combination of vitamin C (which accumulates in hepatoma cells) and a quinone undergoing a redox cycling (vitamin K3) leads to an oxidative stress that kills cancer cells in a selective manner. This differential sensitivity between cancer cells and normal cells may have important clinical applications, as it has been observed with other pro-oxidants like Arsenic trioxide, isothiocyanates, Adaphostin.
Keywords: Antioxidant enzymes, ascorbate, glycolysis, hepatoma, menadione redox cycling, vitamin C uptake
Current Medicinal Chemistry
Title: In Situ Modulation of Oxidative Stress: A Novel and Efficient Strategy to Kill Cancer Cells
Volume: 16 Issue: 15
Author(s): J. Verrax, R. Curi Pedrosa, R. Beck, N. Dejeans, H. Taper and P. Buc Calderon
Affiliation:
Keywords: Antioxidant enzymes, ascorbate, glycolysis, hepatoma, menadione redox cycling, vitamin C uptake
Abstract: Cancer cells show an up-regulation of glycolysis, they readily take up vitamin C, and they appear more susceptible to an oxidative stress than the surrounding normal cells. Here we compare, analyse and discuss these particular hallmarks by performing experiments in murine hepatomas (TLT cells) and freshly isolated mouse hepatocytes. The results show that rates of lactate formation are higher in TLT cells as compared to mouse hepatocytes, but their ATP content represents less than 25% of that in normal cells. The uptake of vitamin C is more important in hepatoma cells as compared to normal hepatocytes. This uptake mainly occurs through GLUT1 transporters. Hepatoma cells have less than 10% of antioxidant enzyme activities as compared to normal hepatocytes. This decrease includes not only the major antioxidant enzymes, namely catalase, superoxide dismutase and glutathione peroxidase, but also the GSH content. Moreover, catalase is almost not expressed in hepatoma cells as shown by western blot analysis. We explored therefore a selective exposure of cancer cells to an oxidative stress induced by pro-oxidant mixtures containing pharmacological doses of vitamin C and a redox active compound such as menadione (vitamin K3). Indeed, the combination of vitamin C (which accumulates in hepatoma cells) and a quinone undergoing a redox cycling (vitamin K3) leads to an oxidative stress that kills cancer cells in a selective manner. This differential sensitivity between cancer cells and normal cells may have important clinical applications, as it has been observed with other pro-oxidants like Arsenic trioxide, isothiocyanates, Adaphostin.
Export Options
About this article
Cite this article as:
Verrax J., Pedrosa Curi R., Beck R., Dejeans N., Taper H. and Calderon Buc P., In Situ Modulation of Oxidative Stress: A Novel and Efficient Strategy to Kill Cancer Cells, Current Medicinal Chemistry 2009; 16 (15) . https://dx.doi.org/10.2174/092986709788186057
DOI https://dx.doi.org/10.2174/092986709788186057 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Are Selenoproteins Important for the Cancer Protective Effects of Selenium?
Current Nutrition & Food Science The Anti-Oxidant Properties of Isothiocyanates: A Review
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery The Role of Co-Infections in Mother-to-Child Transmission of HIV
Current HIV Research Pleiotrophin as a Possible New Target for Angiogenesis-Related Diseases and Cancer
Recent Patents on Anti-Cancer Drug Discovery Vitamin D Receptor is a Novel Drug Target for Ovarian Cancer Treatment
Current Cancer Drug Targets Immunotherapy of Human Cancers Using Gene Modified T Lymphocytes
Current Gene Therapy Using Small Molecule GSK3β Inhibitors to Treat Inflammation
Current Medicinal Chemistry Epidemics and Peptide Vaccine Response: A Brief Review
Current Topics in Medicinal Chemistry DNA Vaccination in Oncology: Current Status, Opportunities and Perspectives
Current Clinical Pharmacology Recent Developments of Nanoparticles in the Treatment of Photodynamic Therapy for Cervical Cancer
Anti-Cancer Agents in Medicinal Chemistry Volatilome Metabolomics and Databases, Recent Advances and Needs
Current Metabolomics Gabapentin and Pregabalin for the Acute Post-operative Pain Management. A Systematic-narrative Review of the Recent Clinical Evidences
Current Drug Targets An Update on Developments in Female Hormonal Contraception
Current Women`s Health Reviews Current Patents on Osteoinductive Molecules for Bone Tissue Engineering
Recent Patents on Biomedical Engineering (Discontinued) Disulfiram's Anticancer Activity: Evidence and Mechanisms
Anti-Cancer Agents in Medicinal Chemistry Colloidal Drug Delivery Systems in Vaccine Delivery
Current Drug Targets Apoptotic Signaling Pathways as a Target for the Treatment of Liver Diseases
Mini-Reviews in Medicinal Chemistry Antibody-directed Double Suicide Gene Therapy Targeting of MUC1- Positive Leukemia Cells In Vitro and In Vivo
Current Gene Therapy Patented Biomarkers of Peripheral Blood for the Early Detection of Cancer
Recent Patents on Biomarkers Anticancer α-Helical Peptides and Structure / Function Relationships Underpinning Their Interactions with Tumour Cell Membranes
Current Protein & Peptide Science