Abstract
The sphingolipids ceramide, sphingosine and sphingosine 1-phosphate have emerged as important signaling molecules that regulate a number of important cellular processes. Sphingosine 1-phosphate enhances cell survival and proliferation, and also regulates angiogenesis, cell invasion, and differentiation via both its cell surface G protein-coupled receptors and recently identified intracellular effectors. In contrast, ceramide and sphingosine elicit growth arrest and apoptosis through direct modulation of a number of intracellular targets. The cellular balance of these sphingolipids contributes to the determination of cell fate, and it is now clear that disruption in this ‘sphingolipid rheostat’ contributes to the development, progression and chemotherapeutic resistance of both hematological malignancies and solid tumors. The sphingosine kinases are central regulators of this pathway since they not only increase sphingosine 1-phosphate and assist in reduction of ceramide and sphingosine, but are also regulated at multiple levels by external stimuli. Thus, targeting the regulation of the sphingosine kinases may be a viable therapeutic strategy for a diverse array of cancers. Here, we describe the current knowledge of sphingosine kinase regulation, effects of current and potential chemotherapeutic agents on this system, and discuss the implications of this for the treatment of hematological malignancies and other cancers.
Keywords: Cancer, Ceramide, Chronic myeloid leukemia, Hematological malignacy, Sphingosine, Sphingosine 1-phosphate, Sphingosine kinase, PKC, CML cells, AML, BCR-ABL, GDNF
Anti-Cancer Agents in Medicinal Chemistry
Title: Regulation of Sphingosine Kinase in Hematological Malignancies and Other Cancers
Volume: 11 Issue: 9
Author(s): Stuart M. Pitson, Jason A. Powell and Claudine S. Bonder
Affiliation:
Keywords: Cancer, Ceramide, Chronic myeloid leukemia, Hematological malignacy, Sphingosine, Sphingosine 1-phosphate, Sphingosine kinase, PKC, CML cells, AML, BCR-ABL, GDNF
Abstract: The sphingolipids ceramide, sphingosine and sphingosine 1-phosphate have emerged as important signaling molecules that regulate a number of important cellular processes. Sphingosine 1-phosphate enhances cell survival and proliferation, and also regulates angiogenesis, cell invasion, and differentiation via both its cell surface G protein-coupled receptors and recently identified intracellular effectors. In contrast, ceramide and sphingosine elicit growth arrest and apoptosis through direct modulation of a number of intracellular targets. The cellular balance of these sphingolipids contributes to the determination of cell fate, and it is now clear that disruption in this ‘sphingolipid rheostat’ contributes to the development, progression and chemotherapeutic resistance of both hematological malignancies and solid tumors. The sphingosine kinases are central regulators of this pathway since they not only increase sphingosine 1-phosphate and assist in reduction of ceramide and sphingosine, but are also regulated at multiple levels by external stimuli. Thus, targeting the regulation of the sphingosine kinases may be a viable therapeutic strategy for a diverse array of cancers. Here, we describe the current knowledge of sphingosine kinase regulation, effects of current and potential chemotherapeutic agents on this system, and discuss the implications of this for the treatment of hematological malignancies and other cancers.
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Cite this article as:
M. Pitson Stuart, A. Powell Jason and S. Bonder Claudine, Regulation of Sphingosine Kinase in Hematological Malignancies and Other Cancers, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (9) . https://dx.doi.org/10.2174/187152011797655078
DOI https://dx.doi.org/10.2174/187152011797655078 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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