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
-
Renin-Angiotensin-Aldosterone System: A Current Drug Target for the Management of Neuropathic Pain
Current Drug Targets Radiation Therapy in the Management of Lung Cancer
Current Respiratory Medicine Reviews Oral HPV Infection: Current Strategies for Prevention and Therapy
Current Pharmaceutical Design Selenium-Rich Foods: a Promising Approach to Colorectal Cancer Prevention
Current Pharmaceutical Biotechnology MET and ALK as Targets for the Treatment of NSCLC
Current Pharmaceutical Design Morin Inhibits Ovarian Cancer Growth through the Inhibition of NF-κB Signaling Pathway
Anti-Cancer Agents in Medicinal Chemistry Targeting the Wingless Signaling Pathway with Natural Compounds as Chemopreventive or Chemotherapeutic Agents
Current Pharmaceutical Biotechnology Clinical Evidence of Herb-Drug Interactions: A Systematic Review by the Natural Standard Research Collaboration
Current Drug Metabolism microRNA-133: Expression, Function and Therapeutic Potential in Muscle Diseases and Cancer
Current Drug Targets Vitamin D: Evolutionary, Physiological and Health Perspectives
Current Drug Targets SALL4: Engine of Cell Stemness
Current Gene Therapy Targeted Cancer Therapy: The Next Generation of Cancer Treatment
Current Drug Discovery Technologies Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure?
Current Diabetes Reviews Alveolar Epithelial Stem and Progenitor Cells: Emerging Evidence for their Role in Lung Regeneration
Current Medicinal Chemistry Cannabinoid Hyperemesis Syndrome
Current Drug Abuse Reviews Metabolic Response Assessment in Non-Small Cell Lung Cancer Patients after Platinum-Based Therapy: A Preliminary Analysis
Current Medical Imaging Remodelling of the Ca2+ Toolkit in Tumor Endothelium as a Crucial Responsible for the Resistance to Anticancer Therapies
Current Signal Transduction Therapy MicroRNAs and Cancer Therapy – From Bystanders to Major Players
Current Medicinal Chemistry When Does Food Refusal Require Professional Intervention?
Current Nutrition & Food Science Editorial
Recent Patents on Inflammation & Allergy Drug Discovery