Altering the Sphingosine-1-Phosphate/Ceramide Balance: A Promising Approach for Tumor Therapy

Authors: Huwiler, Andrea; Pfeilschifter, Josef

Source: Current Pharmaceutical Design, Volume 12, Number 35, December 2006 , pp. 4625-4635(11)

Publisher: Bentham Science Publishers

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Abstract:

In recent years sphingolipids have emerged as important signaling molecules regulating fundamental cell responses such as cell death and differentiation, proliferation and aspects of inflammation. Especially ceramide has been a main focus of research since it possesses pro-apoptotic capacity in many cell types. A counterplayer of ceramide was found in sphingosine-1-phosphate (S1P), which is generated from ceramide by the consecutive actions of ceramidase and sphingosine kinase. S1P can potently induce cell proliferation via binding to and activation of the Edg family of receptors which have now been renamed as S1P receptors. Obviously, a delicate balance between ceramide and sphingosine-1- phosphate determines whether cells undergo apoptosis or proliferate, two cell responses that are critically involved in tumor development. Directing the balance in favor of ceramide, i.e. by inhibiting ceramidase or sphingosine kinase activities may support the pro-apoptotic action of ceramide and thus may have beneficial effects in cancer therapy. This review will summarize novel insights into the regulation of sphingolipid formation and their potential involvement in tumor development. Finally, we will pinpoint potential new targets for tumor therapy.

Keywords: sphinganine; Ceramide; protein kinase B; Apoptosis; Cell Proliferation; Angiogenesis; FTY720

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161206779010422

Affiliations: 1: Pharmazentrum frankfurt,Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.

Publication date: 2006-12-01

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Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

Altering the Sphingosine-1-Phosphate/Ceramide Balance: A Promising Approach for Tumor Therapy

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