Abstract
Sphingolipids comprise a family of bioactive lipids that exert antagonizing roles in diverse cellular functions such as cell proliferation, growth arrest or apoptosis. Synthesized in the ER/Golgi, sphingolipids are subsequently distributed to different compartments, most predominantly in the plasma membrane, where they integrate signaling platforms. In addition to its precursor role in the synthesis of complex glycosphingolipids, ceramide has been identified as a cell death effector and its generation increases in response to apoptotic stimuli including stress, radiation, chemotherapy, and death ligands. In contrast, sphingosine-1-phosphate (S1P) has been mainly characterized as an antiapoptotic sphingolipid mediating cell proliferation and survival. Thus, the relative balance between ceramide and SIP has important implications in disease pathogenesis, and therefore the pharmacological modulation of enzymes involved in regulation of the ceramide to SIP ratio could constitute a novel therapeutic approach for the treatment of human diseases and cancer.
Keywords: Ceramide, sphingosine-1-phosphate, mitochondria, apoptosis, necrosis, cancer therapy
Mini-Reviews in Medicinal Chemistry
Title: Pharmacological Modulation of Sphingolipids and Role in Disease and Cancer Cell Biology
Volume: 7 Issue: 4
Author(s): Albert Morales and Jose C. Fernandez-Checa
Affiliation:
Keywords: Ceramide, sphingosine-1-phosphate, mitochondria, apoptosis, necrosis, cancer therapy
Abstract: Sphingolipids comprise a family of bioactive lipids that exert antagonizing roles in diverse cellular functions such as cell proliferation, growth arrest or apoptosis. Synthesized in the ER/Golgi, sphingolipids are subsequently distributed to different compartments, most predominantly in the plasma membrane, where they integrate signaling platforms. In addition to its precursor role in the synthesis of complex glycosphingolipids, ceramide has been identified as a cell death effector and its generation increases in response to apoptotic stimuli including stress, radiation, chemotherapy, and death ligands. In contrast, sphingosine-1-phosphate (S1P) has been mainly characterized as an antiapoptotic sphingolipid mediating cell proliferation and survival. Thus, the relative balance between ceramide and SIP has important implications in disease pathogenesis, and therefore the pharmacological modulation of enzymes involved in regulation of the ceramide to SIP ratio could constitute a novel therapeutic approach for the treatment of human diseases and cancer.
Export Options
About this article
Cite this article as:
Morales Albert and Fernandez-Checa C. Jose, Pharmacological Modulation of Sphingolipids and Role in Disease and Cancer Cell Biology, Mini-Reviews in Medicinal Chemistry 2007; 7 (4) . https://dx.doi.org/10.2174/138955707780363792
DOI https://dx.doi.org/10.2174/138955707780363792 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
- 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
-
Nucleic Acid Aptamers Against Protein Kinases
Current Medicinal Chemistry Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy
Current Gene Therapy Vascularization of Biomaterials for Bone Tissue Engineering: Current Approaches and Major Challenges
Current Angiogenesis (Discontinued) Molecular Analysis of the In Vivo Metabolism and Biodistribution of Metabolically and Non-Metabolically Activated Combi-Molecules of the Triazene Class
Drug Metabolism Letters Recent Advances of MEK Inhibitors and Their Clinical Progress
Current Topics in Medicinal Chemistry Cyclooxygenase-2 (COX-2) Mediates Arsenite Inhibition of UVB-Induced Cellular Apoptosis in Mouse Epidermal Cl41 Cells
Current Cancer Drug Targets Apoptosis-Inducing Effects of Amaryllidaceae Alkaloids
Current Medicinal Chemistry Editorial (Thematic Issue: Self-Assembled Organic Nanostructures in Medicinal Chemistry: Advances and Applications)
Current Topics in Medicinal Chemistry Oncolytic Virus Therapy - Foreword
Current Cancer Drug Targets Recent Advances in the Use of Metallic Nanoparticles with Antitumoral Action - Review
Current Medicinal Chemistry Superparamagnetic Magnetite (Fe3O4) Nanoparticles for Bio-Applications
Recent Patents on Materials Science In Vivo Apoptosis Imaging Agents and Strategies
Anti-Cancer Agents in Medicinal Chemistry Understanding Cancer Drug Resistance by Developing and Studying Resistant Cell Line Models
Current Cancer Drug Targets Astrocytes as an HIV Reservoir: Mechanism of HIV Infection
Current HIV Research Proteomics Annotation of Lipid Rafts Modified by Virus Infection
Combinatorial Chemistry & High Throughput Screening Hologram QSAR Studies of N,N-Dialkyl-2-phenylindol-3-ylglyoxylamides Derivatives as Selective Peripheral Benzodiazepine Receptor Ligands
Letters in Drug Design & Discovery Natural Compounds with Proteasome Inhibitory Activity for Cancer Prevention and Treatment
Current Protein & Peptide Science Nanotechnology Based Theranostic Approaches in Alzheimer's Disease Management: Current Status and Future Perspective
Current Alzheimer Research Epigenetics in Clinical Management of Children and Adolescents with Brain Tumors
Current Cancer Drug Targets Poly (ADP-Ribosyl) Polymerase 1 Inhibitors: A Patent Review
Recent Patents on Anti-Cancer Drug Discovery