Abstract
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
Anti-Cancer Agents in Medicinal Chemistry
Title:Alteration of Ceramide 1-O-Functionalization as a Promising Approach for Cancer Therapy
Volume: 12 Issue: 4
Author(s): Stephanie Ballereau, Thierry Levade, Yves Genisson and Nathalie Andrieu-Abadie
Affiliation:
Keywords: Apoptosis, Ceramide, Inhibitors, Metabolism, Sphingolipids, Tumor, SL metabolism, ceramide metabolic pathway, GSLs
Abstract: 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.
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Ballereau Stephanie, Levade Thierry, Genisson Yves and Andrieu-Abadie Nathalie, Alteration of Ceramide 1-O-Functionalization as a Promising Approach for Cancer Therapy , Anti-Cancer Agents in Medicinal Chemistry 2012; 12 (4) . https://dx.doi.org/10.2174/187152012800228634
DOI https://dx.doi.org/10.2174/187152012800228634 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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