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Spotlight on Molecular Targeted Therapy

Sphingosine 1-phosphate as a therapeutic agent

Leukemia volume 16, pages 1596–1602 (2002)Cite this article

Abstract

The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P), formed by activation of sphingosine kinase in response to diverse stimuli, is an important lipid mediator that has novel dual actions – both inside and outside of cells. S1P is the ligand for a family of five G protein-coupled receptors. Activation of these GPCRs by S1P or dihydro-S1P regulates diverse processes, including cell migration, angiogenesis, vascular maturation, heart development, and neurite retraction. There is also abundant evidence that S1P can function as a second messenger important for regulation of calcium homeostasis, cell growth, and suppression of apoptosis. In many cases, the intracellular level of S1P and ceramide, another important sphingolipid metabolite associated with cell death and cell growth arrest, coordinately determine cell fate. Changes in S1P and ceramide have been implicated in a number of pathological conditions in which apoptosis plays an important role. Importantly, radiation-induced oocyte loss in adult female mice, the event that drives premature ovarian failure and infertility in female cancer patients, was completely prevented by in vivotherapy with S1P. Understanding the biosynthesis, metabolism and functions of S1P can uncover new targets for the pharmaceutical and therapeutic applications of S1P.

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Acknowledgements

This work was supported by National Institutes of Health Grants GM43880 and CA61774 (to SS) and CA85704 and CA42385 (to RK).

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  1. Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA

    S Spiegel

  2. Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    R Kolesnick

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Spiegel, S., Kolesnick, R. Sphingosine 1-phosphate as a therapeutic agent. Leukemia 16, 1596–1602 (2002). https://doi.org/10.1038/sj.leu.2402611

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