Abstract
Sphingolipids, which are complex lipidic components of the cell membranes, lie in a key position to modulate the pathways of trans-membrane signaling and allow the cell to adapt to environmental stresses. In malignancies, reduced production of some sphingolipid species able to induce apoptosis such as ceramide and conversely, increased levels of some other metabolites involved in tumor progression and drug resistance of cancer cells, are often described. In this context, the discovery of new chemical entities able to specifically modify ceramide metabolism should offer novel pharmacological tools in cancer therapy.
The review dedicates particular attention to the enzymes that modify ceramide at the C1-OH position generating other biologically important sphingolipids in cancer, such as sphingomyelin, ceramide-1-phosphate or glucosylceramide. Findings reported in the literature leading to the development of new chemical entities specifically designed to achieve the above goals have been collected and are discussed. The effects of enzyme inhibitors of sphingomyelin synthase, ceramide kinase and glucosylceramide synthase on cancer cell proliferation, sensitivity to chemotherapeutics, induction of apoptosis or growth of xenografts are presented.
Keywords: Apoptosis, Ceramide, Inhibitors, Metabolism, Sphingolipids, Tumor, SL metabolism, ceramide metabolic pathway, GSLs
Anti-Cancer Agents in Medicinal Chemistry
Title:Alteration of Ceramide 1-O-Functionalization as a Promising Approach for Cancer Therapy
Volume: 12 Issue: 4
Author(s): Stephanie Ballereau, Thierry Levade, Yves Genisson and Nathalie Andrieu-Abadie
Affiliation:
Keywords: Apoptosis, Ceramide, Inhibitors, Metabolism, Sphingolipids, Tumor, SL metabolism, ceramide metabolic pathway, GSLs
Abstract: Sphingolipids, which are complex lipidic components of the cell membranes, lie in a key position to modulate the pathways of trans-membrane signaling and allow the cell to adapt to environmental stresses. In malignancies, reduced production of some sphingolipid species able to induce apoptosis such as ceramide and conversely, increased levels of some other metabolites involved in tumor progression and drug resistance of cancer cells, are often described. In this context, the discovery of new chemical entities able to specifically modify ceramide metabolism should offer novel pharmacological tools in cancer therapy.
The review dedicates particular attention to the enzymes that modify ceramide at the C1-OH position generating other biologically important sphingolipids in cancer, such as sphingomyelin, ceramide-1-phosphate or glucosylceramide. Findings reported in the literature leading to the development of new chemical entities specifically designed to achieve the above goals have been collected and are discussed. The effects of enzyme inhibitors of sphingomyelin synthase, ceramide kinase and glucosylceramide synthase on cancer cell proliferation, sensitivity to chemotherapeutics, induction of apoptosis or growth of xenografts are presented.
Export Options
About this article
Cite this article as:
Ballereau Stephanie, Levade Thierry, Genisson Yves and Andrieu-Abadie Nathalie, Alteration of Ceramide 1-O-Functionalization as a Promising Approach for Cancer Therapy , Anti-Cancer Agents in Medicinal Chemistry 2012; 12 (4) . https://dx.doi.org/10.2174/187152012800228634
DOI https://dx.doi.org/10.2174/187152012800228634 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
- 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
-
Resistance to Imatinib in Chronic Myeloid Leukemia and Therapeutic Approaches to Circumvent the Problem
Cardiovascular & Hematological Disorders-Drug Targets Structural and Functional Organization of miRNAs
Current Pharmacogenomics Interleukin-24: A Molecule with Potential Anti-Cancer Activity and a Cytokine in Search of a Function
Endocrine, Metabolic & Immune Disorders - Drug Targets Small Molecule Aurora Kinases Inhibitors
Current Medicinal Chemistry From Amino Acids to Proteins as Targets for Metal-based Drugs
Current Drug Metabolism Exploring Confluence-Related Signalling to Modulate the Expression of Oct4 – A Role in Facilitating Mouse Somatic Cell Reprogramming?
Current Stem Cell Research & Therapy Targeting Epigenetics through Histone Deacetylase Inhibitors in Acute Lymphoblastic Leukemia
Current Cancer Drug Targets Iron Chelating Strategies in Systemic Metal Overload, Neurodegeneration and Cancer
Current Medicinal Chemistry Synthesis, Characterization by Means of IR, 1H, 13C - NMR and Biological Investigations on New Diorganotin Carboxylic Acid Derivatives
Letters in Drug Design & Discovery Structure-activity Relationship Studies of New Marine Anticancer Agents and their Synthetic Analogues
Current Medicinal Chemistry Measurement of Vitamin K Metabolites in Neonatal Faecal Matter by HPLC with Electrochemical Detection
Current Chromatography Ribonucleases, Nucleases and Antiangiogenins in Antiproliferative Activities
Current Signal Transduction Therapy Triggering PIK3CA Mutations in PI3K/Akt/mTOR Axis: Exploration of Newer Inhibitors and Rational Preventive Strategies
Current Pharmaceutical Design Kit: Molecule of Interest for the Diagnosis and Treatment of Mastocytosis and other Neoplastic Disorders
Current Cancer Drug Targets Dasatinib: An Anti-Tumour Agent via Src Inhibition
Current Drug Targets Molecular Mechanisms Responsible for <i>In Vitro</i> Cytotoxic Attributes of <i>Conyza bonariensis</i> Extract against Lymphoblastic Leukaemia Jurkat Cells
Anti-Cancer Agents in Medicinal Chemistry Recent Research Trends on Bismuth Compounds in Cancer Chemoand Radiotherapy
Current Medicinal Chemistry Promises of Apoptosis-Inducing Peptides in Cancer Therapeutics
Current Pharmaceutical Biotechnology Prognostic Parameters in Myeloid Malignancies in a Historical Context – From Microscopy to Individualized Medicine
Current Drug Targets Immunoglobulin Free Light Chains in Immune Responses
Current Immunology Reviews (Discontinued)