Abstract
Therapeutic induction of apoptosis is an important goal of anti-cancer drug design. Here, we review briefly the emerging role of cellular carbonyl stress in melanoma proliferative control, antiapoptotic survival signaling, progression, and metastasis. Cellular carbonyl stress mediated by endogenous reactive carbonyl species (RCS) such as glyoxal, methylglyoxal (MG), and malondialdehyde has been implicated in proliferative signaling and metastasis of human tumor cells. RCS-derived protein-epitopes called advanced glycation endproducts (AGEs) formed from chemical reaction between RCS and tissue proteins are abundant in melanoma tissue, and AGEs are potent ligands of RAGE, a membrane receptor involved in melanoma proliferation and metastasis. In addition to the established role of AGE-RAGE signaling in many human malignancies, increasing experimental evidence supports the hypothesis that RCS, originating from increased tumor cell glycolysis and mitochondrial oxidative stress, are small molecular anti-apoptotic effectors targeting the mitochondrial permeability transition pore (MPTP). We also discuss the emerging role of RCS as novel molecular targets for chemotherapeutic intervention, and provide preliminary experimental evidence that carbonyl scavengers, specific molecular antagonists of RCS, may represent a novel class of anti-melanoma therapeutics.
Keywords: apoptosis, carbonyl scavenger, carbonyl stress, melanoma, mitochondrial permeability transition pore, receptor for advanced glycation endproducts
Current Cancer Therapy Reviews
Title: An Emerging Molecular Target in Melanoma: Cellular Carbonyl Stress and the Inhibition of Mitochondrial Survival Pathways by Carbonyl Scavenger Agents
Volume: 1 Issue: 3
Author(s): Georg T. Wondrak, Myron K. Jacobson and Elaine L. Jacobson
Affiliation:
Keywords: apoptosis, carbonyl scavenger, carbonyl stress, melanoma, mitochondrial permeability transition pore, receptor for advanced glycation endproducts
Abstract: Therapeutic induction of apoptosis is an important goal of anti-cancer drug design. Here, we review briefly the emerging role of cellular carbonyl stress in melanoma proliferative control, antiapoptotic survival signaling, progression, and metastasis. Cellular carbonyl stress mediated by endogenous reactive carbonyl species (RCS) such as glyoxal, methylglyoxal (MG), and malondialdehyde has been implicated in proliferative signaling and metastasis of human tumor cells. RCS-derived protein-epitopes called advanced glycation endproducts (AGEs) formed from chemical reaction between RCS and tissue proteins are abundant in melanoma tissue, and AGEs are potent ligands of RAGE, a membrane receptor involved in melanoma proliferation and metastasis. In addition to the established role of AGE-RAGE signaling in many human malignancies, increasing experimental evidence supports the hypothesis that RCS, originating from increased tumor cell glycolysis and mitochondrial oxidative stress, are small molecular anti-apoptotic effectors targeting the mitochondrial permeability transition pore (MPTP). We also discuss the emerging role of RCS as novel molecular targets for chemotherapeutic intervention, and provide preliminary experimental evidence that carbonyl scavengers, specific molecular antagonists of RCS, may represent a novel class of anti-melanoma therapeutics.
Export Options
About this article
Cite this article as:
Wondrak T. Georg, Jacobson K. Myron and Jacobson L. Elaine, An Emerging Molecular Target in Melanoma: Cellular Carbonyl Stress and the Inhibition of Mitochondrial Survival Pathways by Carbonyl Scavenger Agents, Current Cancer Therapy Reviews 2005; 1 (3) . https://dx.doi.org/10.2174/157339405774574234
DOI https://dx.doi.org/10.2174/157339405774574234 |
Print ISSN 1573-3947 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6301 |
Call for Papers in Thematic Issues
Current progress in Protein Degradation and Cancer Therapy
argeted Protein Degradation is gaining momentum in cancer therapy, it facilitate targeting undruggable proteins, it overcome cancer resistance and avoid undesirable side effects. Thus small molecules degraders have emerged as novel therapeutic strategy. Targeted protein degradation (TPD), the process of eliminating a protein of interest hold a great promise for ...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
-
Development of a Novel Reporter Gene Vector for Cell Based Angiogenic Studies
Combinatorial Chemistry & High Throughput Screening Alpha-Particle Microdosimetry
Current Radiopharmaceuticals Sphingolipid Metabolism and Drug Resistance in Hematological Malignancies
Anti-Cancer Agents in Medicinal Chemistry Reproductive and Endocrine Effects of p-Nonylphenol and Methoxychlor: A Review
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Ansamycin Inhibitors of Hsp90: Natures Prototype for Anti-Chaperone Therapy
Current Topics in Medicinal Chemistry A Unique Intracellular, Extracellular and Transmembrane Circulation of Potassium Ions in the Auditory Inner Ear as an Anticarcinogenic Principle? Part 1
Inflammation & Allergy - Drug Targets (Discontinued) Trichothecenes: Structure-Toxic Activity Relationships
Current Drug Metabolism Bleomycin Induced Sensitivity to TRAIL/Apo-2L-Mediated Apoptosis in Human Seminomatous Testicular Cancer Cells is Correlated with Upregulation of Death Receptors
Anti-Cancer Agents in Medicinal Chemistry Metastasis-Associated Protein S100A4: Spotlight on its Role in Cell Migration
Current Cancer Drug Targets Role of Chromatography for Monitoring of Breast Cancer Biomarkers
Recent Patents on Biomarkers Macrocyclic Inhibitors of Hsp90
Current Topics in Medicinal Chemistry Antibody-Drug Conjugate Targets
Current Cancer Drug Targets Preclinical Development of Novel Anti-Glioma Drugs Targeting the Endoplasmic Reticulum Stress Response
Current Pharmaceutical Design Stem Cells: An Overview of the Current Status of Therapies for Central and Peripheral Nervous System Diseases
Current Medicinal Chemistry Recent Trends in Glycodendrimer Syntheses and Applications
Current Topics in Medicinal Chemistry The Forkhead Transcription Factor FOXO3a Controls Microglial Inflammatory Activation and Eventual Apoptotic Injury through Caspase 3
Current Neurovascular Research Development of Curcumin-Loaded Solid Lipid Nanoparticles Utilizing Glyceryl Monostearate as Single Lipid Using QbD Approach: Characterization and Evaluation of Anticancer Activity Against Human Breast Cancer Cell Line
Current Drug Delivery Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway
Clinical Cancer Drugs Reactive Oxygen Species, Cancer and Anti-Cancer Therapies
Current Chemical Biology A Personalized Approach to Systemic Treatment of Unresectable or Metastatic Pancreatic Adenocarcinoma
Current Pharmacogenomics and Personalized Medicine