Abstract
Sphingolipids (SLs) and cholesterol are critical structural components of membrane bilayers. Although recent evidence has revealed an emerging role of both lipids in signaling pathways, their contribution to cancer development and treatment has been largely overlooked. Sphingolipids comprise a family of bioactive lipids with divergent roles in numerous cellular processes. In particular, ceramide is the prototype of SLs and identified as a cell death effector whose levels increase in response to apoptotic stimuli such as ionizing radiation or chemotherapy. In the liver, ceramide/cholesterol accumulation contributes to a wide range of pathologies, including the transition from steatosis to steatohepatitis, which can further progress to cirrhosis and hepatocellular carcinoma (HCC). Moreover, different studies have shown that either pharmacologic ceramide accumulation or systemic intravenous administration of liposomal ceramide is an effective approach against HCC. In addition, mitochondrial cholesterol trafficking has emerged as a novel factor regulating cell death pathways and HCC tumor growth and chemoresistance. Due to the poor efficacy of current HCC treatments, understanding the role of ceramide/cholesterol in HCC may open up novel avenues for therapy. Here we describe recent evidence indicating that ceramide-generating agents and/or pharmacological targeting of sphingolipid/cholesterol metabolism, alone or in combination with other chemotherapeutic compounds, may be a promising strategy in HCC management.
Keywords: Mitochondria, Ceramide, Cancer cell biology, Chemotherapy, sphingomyelinases, ceramide and gangliosides, pro-apoptotic ceramides, chemotherapeutic agents, pathologies, transmembrane protein, Cholesterol
Anti-Cancer Agents in Medicinal Chemistry
Title:Hepatocarcinogenesis and Ceramide/Cholesterol Metabolism
Volume: 12 Issue: 4
Author(s): Albert Morales, Montserrat Mari, Carmen Garcia-Ruiz, Anna Colell and Jose C. Fernandez-Checa
Affiliation:
Keywords: Mitochondria, Ceramide, Cancer cell biology, Chemotherapy, sphingomyelinases, ceramide and gangliosides, pro-apoptotic ceramides, chemotherapeutic agents, pathologies, transmembrane protein, Cholesterol
Abstract: Sphingolipids (SLs) and cholesterol are critical structural components of membrane bilayers. Although recent evidence has revealed an emerging role of both lipids in signaling pathways, their contribution to cancer development and treatment has been largely overlooked. Sphingolipids comprise a family of bioactive lipids with divergent roles in numerous cellular processes. In particular, ceramide is the prototype of SLs and identified as a cell death effector whose levels increase in response to apoptotic stimuli such as ionizing radiation or chemotherapy. In the liver, ceramide/cholesterol accumulation contributes to a wide range of pathologies, including the transition from steatosis to steatohepatitis, which can further progress to cirrhosis and hepatocellular carcinoma (HCC). Moreover, different studies have shown that either pharmacologic ceramide accumulation or systemic intravenous administration of liposomal ceramide is an effective approach against HCC. In addition, mitochondrial cholesterol trafficking has emerged as a novel factor regulating cell death pathways and HCC tumor growth and chemoresistance. Due to the poor efficacy of current HCC treatments, understanding the role of ceramide/cholesterol in HCC may open up novel avenues for therapy. Here we describe recent evidence indicating that ceramide-generating agents and/or pharmacological targeting of sphingolipid/cholesterol metabolism, alone or in combination with other chemotherapeutic compounds, may be a promising strategy in HCC management.
Export Options
About this article
Cite this article as:
Morales Albert, Mari Montserrat, Garcia-Ruiz Carmen, Colell Anna and Fernandez-Checa Jose C., Hepatocarcinogenesis and Ceramide/Cholesterol Metabolism , Anti-Cancer Agents in Medicinal Chemistry 2012; 12 (4) . https://dx.doi.org/10.2174/187152012800228689
DOI https://dx.doi.org/10.2174/187152012800228689 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
Glycogen Synthase Kinase 3 as an Anticancer Drug Target: Novel Experimental Findings and Trends in the Design of Inhibitors
Current Pharmaceutical Design Phase I Clinical Trial of Exherin (ADH-1) in Patients with Advanced Solid Tumors
Current Clinical Pharmacology Immunomodulation and Anti-inflammatory Roles of Polyphenols as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids
Current Topics in Medicinal Chemistry Optimization of the Enzymolysis Conditions for Scorpion Peptides and Evaluation of its Antitumor Activity
Current Signal Transduction Therapy Isoprenylation of Intracellular Proteins as a New Target for the Therapy of Human Neoplasms: Preclinical and Clinical Implications
Current Drug Targets Prokinetic Agents and QT Prolongation: A Familiar Scene with New Actors
Current Drug Safety Epidemiology of Major Congenital Malformations with Specific Focus on Teratogens
Current Drug Safety Risk Factors for Upper GI Damage in Low-Dose Aspirin Users and the Interaction Between <i>H. pylori</i> Infection and Low-Dose Aspirin Use
Current Pharmaceutical Design Nanocrystal Technology in the Delivery of Poorly Soluble Drugs: An Overview
Current Drug Delivery Advances in Drug Safety
Current Pharmaceutical Design Therapeutic and Diagnostic Applications of Nanoparticles
Current Drug Targets Budesonide and Phenethyl Isothiocyanate Attenuate DNA Damage in Bronchoalveolar Lavage Cells of Mice Exposed to Environmental Cigarette Smoke
Current Cancer Drug Targets An Overview of Nano Delivery Systems for Targeting RNA Interference-based Therapy in Ulcerative Colitis
Current Pharmaceutical Design Current Protein-based Anti-angiogenic Therapeutics
Mini-Reviews in Medicinal Chemistry MicroRNA-21: From Cancer to Cardiovascular Disease
Current Drug Targets A Comprehensive Study of Pharmacological Behaviors, Nano-Formulations, and Applications of Rosemary
The Natural Products Journal Discovery and Development of Natural Products and their Derivatives as Photosensitizers for Photodynamic Therapy
Current Medicinal Chemistry Biosafety Challenges for Use of Lentiviral Vectors in Gene Therapy
Current Gene Therapy HGF/MET Signaling in Ovarian Cancer
Current Molecular Medicine