Abstract
Co-Administration of CuII chelates are reported to decrease life threatening Cisplatin [PtII(NH3)2(CL)2]-induced acute degenerative renal, gastrointestinal, thymic, and bone marrow states consistent with serious necrotizing and immunemediated inflammatory disease. Initially it was found that copper sulfate treatment completely prevented lethality as well as gastric and nephrotoxicity without compromising PtII(NH3)2(CL)2 antineoplastic activity, which led to suggestions that prior CuIItreatment be used clinically to prevent serious side effects of PtII(NH3)2(CL)2-treatment. In the course of these studies it was discovered that CuII-treatments alone inhibited neoplastic growth and increased survival of rat and mouse models of cancer. Subsequently it was discovered that a stable non-toxic and non-polar lipophilic chelate, CopperII 2(3,5-diisopropylsalicylate)4, caused redifferentiation of cultured neuroblastoma and mouse muscle-implanted mammary adenocarcinoma without neoplastic cell killing. Another stable non-toxic and non-polar lipophilic chelate, CopperII 2(3,5-ditertiarybutylsalicylate)4, was found to prevent Bax-initiated and caspases-3-activation mediated apoptosis. These remarkable observations are concluded to be due to enzyme-mimetic or modulating reactivities of CuII chelates and/or facilitation of CuII or I-dependent enzyme syntheses required to overcome inflammatory-neoplastic disease states. Further, approaches to treating neoplastic diseases by removal of Cu from tissues with ammonium tetrathiomolybdate in an anticopper approach to therapy are not well founded based upon existing scientific literature.
Keywords: Cisplatin, anticancer, copper chelates, redifferentiation, anti-inflammatory, ammonium tetrathiomolybdate, coppertetrathiomolybdate, androstenedione synthesis
Current Medicinal Chemistry
Title:Co-Treatment With Copper Compounds Dramatically Decreases Toxicities Observed With Cisplatin Cancer Therapy And The Anticancer Efficacy Of Some Copper Chelates Supports The Conclusion That Copper Chelate Therapy May Be Markedly More Effective And Less Toxic Than Cisplatin Therapy
Volume: 14 Issue: 14
Author(s): John R. J. Sorenson and Grant W. Wangila
Affiliation:
Keywords: Cisplatin, anticancer, copper chelates, redifferentiation, anti-inflammatory, ammonium tetrathiomolybdate, coppertetrathiomolybdate, androstenedione synthesis
Abstract: Co-Administration of CuII chelates are reported to decrease life threatening Cisplatin [PtII(NH3)2(CL)2]-induced acute degenerative renal, gastrointestinal, thymic, and bone marrow states consistent with serious necrotizing and immunemediated inflammatory disease. Initially it was found that copper sulfate treatment completely prevented lethality as well as gastric and nephrotoxicity without compromising PtII(NH3)2(CL)2 antineoplastic activity, which led to suggestions that prior CuIItreatment be used clinically to prevent serious side effects of PtII(NH3)2(CL)2-treatment. In the course of these studies it was discovered that CuII-treatments alone inhibited neoplastic growth and increased survival of rat and mouse models of cancer. Subsequently it was discovered that a stable non-toxic and non-polar lipophilic chelate, CopperII 2(3,5-diisopropylsalicylate)4, caused redifferentiation of cultured neuroblastoma and mouse muscle-implanted mammary adenocarcinoma without neoplastic cell killing. Another stable non-toxic and non-polar lipophilic chelate, CopperII 2(3,5-ditertiarybutylsalicylate)4, was found to prevent Bax-initiated and caspases-3-activation mediated apoptosis. These remarkable observations are concluded to be due to enzyme-mimetic or modulating reactivities of CuII chelates and/or facilitation of CuII or I-dependent enzyme syntheses required to overcome inflammatory-neoplastic disease states. Further, approaches to treating neoplastic diseases by removal of Cu from tissues with ammonium tetrathiomolybdate in an anticopper approach to therapy are not well founded based upon existing scientific literature.
Export Options
About this article
Cite this article as:
J. Sorenson R. John and Wangila W. Grant, Co-Treatment With Copper Compounds Dramatically Decreases Toxicities Observed With Cisplatin Cancer Therapy And The Anticancer Efficacy Of Some Copper Chelates Supports The Conclusion That Copper Chelate Therapy May Be Markedly More Effective And Less Toxic Than Cisplatin Therapy, Current Medicinal Chemistry 2007; 14 (14) . https://dx.doi.org/10.2174/092986707780831041
DOI https://dx.doi.org/10.2174/092986707780831041 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
Members of CRF Family and their Receptors: From Past to Future
Current Medicinal Chemistry Activin and TGF-β Effects on Brain Development and Neural Stem Cells
CNS & Neurological Disorders - Drug Targets Carotenoids of Microalgae Used in Food Industry and Medicine
Mini-Reviews in Medicinal Chemistry Gene Therapy Targeting in the Central Nervous System
Current Gene Therapy Relevance of Protein Isoforms in Proteomic Studies
Current Proteomics Polyphenols: Well Beyond The Antioxidant Capacity: Gallic Acid and Related Compounds as Neuroprotective Agents: You are What You Eat!
Current Pharmaceutical Biotechnology Dendritic Cells in Colorectal Cancer and a Potential for their Use in Therapeutic Approaches
Current Pharmaceutical Design Targeting Phospho-Ser422 by Active Tau Immunotherapy in the THYTau22 Mouse Model: A Suitable Therapeutic Approach
Current Alzheimer Research Ethanol Metabolism and Effects: Nitric Oxide and its Interaction
Current Clinical Pharmacology Electrical Impedance Scanning - A New Diagnostic Tool in Cancer Detection: Current Status and Recent Developments
Current Medical Imaging HLA-G Expression in Cancers: Potential Role in Diagnosis, Prognosis and Therapy
Endocrine, Metabolic & Immune Disorders - Drug Targets Beneficial Neurobiological Effects of Melatonin Under Conditions of Increased Oxidative Stress
Current Medicinal Chemistry - Central Nervous System Agents Activation of Sphingosine Kinase-1 in Cancer: Implications for Therapeutic Targeting
Current Molecular Pharmacology Role of Lipid Rafts/Caveolae in the Anticancer Effect of Endocannabinoids
Mini-Reviews in Medicinal Chemistry Parkinson’s Disease and Alpha-Synucleinopathies: from Arising Pathways to Therapeutic Challenge
Central Nervous System Agents in Medicinal Chemistry Zebrafish as a Model System to Screen Radiation Modifiers
Current Genomics Survivin: Role in Normal Cells and in Pathological Conditions
Current Cancer Drug Targets Inhibitors of Catechol-O-Methyltransferase
CNS & Neurological Disorders - Drug Targets The Role of Vasopressin in Affective Disorders: Possible Targets of Intervention
Central Nervous System Agents in Medicinal Chemistry Vitamin E - Occurrence, Biosynthesis by Plants and Functions in Human Nutrition
Mini-Reviews in Medicinal Chemistry