Alteration of Ceramide 1-O-Functionalization as a Promising Approach for Cancer Therapy

Author(s): Stephanie Ballereau, Thierry Levade, Yves Genisson, Nathalie Andrieu-Abadie

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 12 , Issue 4 , 2012

Become EABM
Become Reviewer
Call for Editor


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

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2012
Published on: 19 April, 2012
Page: [316 - 328]
Pages: 13
DOI: 10.2174/187152012800228634
Price: $65

Article Metrics

PDF: 13