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

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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  • 27th of 59 in Chemistry, Medicinal

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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



Anti-Cancer Agents in Medicinal Chemistry, 12(4): 316-328.

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

Affiliation: (YG) SPCMIB, UMR CNRS 5068, 118, route de Narbonne, Universite Paul Sabatier, Toulouse Cedex 9 France.

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 .



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Article Details

Volume: 12
Issue Number: 4
First Page: 316
Last Page: 328
Page Count: 13
DOI: 10.2174/187152012800228634
Price: $58
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