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 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
-
The Pathophysiological Role of PEDF in Bone Diseases
Current Molecular Medicine Editorial [Hot Topic: New Approaches to Treating Cancer: Medicinal Chemistry and Therapeutic Potential (Guest Editor: David J. Weber)]
Current Topics in Medicinal Chemistry Anticancer Drug Design Using Scaffolds of β-Lactams, Sulfonamides, Quinoline, Quinoxaline and Natural Products. Drugs Advances in Clinical Trials
Current Medicinal Chemistry Pregnancy, Programming and Preeclampsia: Gap Junctions at the Nexus of Pregnancy-induced Adaptation of Endothelial Function and Endothelial Adaptive Failure in PE
Current Vascular Pharmacology Targeting Histone Deacetylases in Neuroblastoma
Current Pharmaceutical Design Aluminum Vaccine Adjuvants: Are they Safe?
Current Medicinal Chemistry Photo- and Sono-Dynamic Therapy: A Review of Mechanisms and Considerations for Pharmacological Agents Used in Therapy Incorporating Light and Sound
Current Pharmaceutical Design Organoselenium Compounds in Cancer Chemoprevention
Mini-Reviews in Medicinal Chemistry Brain Proton Magnetic Resonance Spectroscopy: A Review of Main Metabolites and its Clinical Applications in Gliomas
Current Molecular Imaging (Discontinued) Base Excision Repair: Contribution to Tumorigenesis and Target in Anticancer Treatment Paradigms
Current Medicinal Chemistry Thrombospondin and Apoptosis: Molecular Mechanisms and Use for Design of Complementation Treatments
Current Drug Targets Application of dsRNA in Cancer Immunotherapy: Current Status and Future Trends
Anti-Cancer Agents in Medicinal Chemistry Early Genetic Changes Involved in Low-Grade Astrocytic Tumor Development
Current Molecular Medicine Serum miRNAs Signature Plays an Important Role in Keloid Disease
Current Molecular Medicine Lipid-Based Vectors for Therapeutic mRNA-Based Anti-Cancer Vaccines
Current Pharmaceutical Design ABC Transporters in Multidrug Resistance and Pharmacokinetics, and Strategies for Drug Development
Current Pharmaceutical Design Melanoma Differentiation Associated Gene-7 (mda-7)/ Interleukin-24 (IL-24), mda-7/IL-24: Current Perspectives on a Unique Member of the IL-10 Family of Cytokines
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Effect of Curcumin on Pro-angiogenic Factors in the Xenograft Model of Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in Formation, Properties, and Applications of Polymersomes
Current Pharmaceutical Design COX-2, Cell Proliferation and PMA in Head-and-Neck Cancer Cells
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued)