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Review
. 2013 Aug;5(12):1405-21.
doi: 10.4155/fmc.13.107.

A Review of Ceramide Analogs as Potential Anticancer Agents

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Free PMC article
Review

A Review of Ceramide Analogs as Potential Anticancer Agents

Jiawang Liu et al. Future Med Chem. .
Free PMC article

Abstract

Ceramide serves as a central mediator in sphingolipid metabolism and signaling pathways, regulating many fundamental cellular responses. It is referred to as a 'tumor suppressor lipid', since it powerfully potentiates signaling events that drive apoptosis, cell cycle arrest, and autophagic responses. In the typical cancer cell, ceramide levels and signaling are usually suppressed by overexpression of ceramide-metabolizing enzymes or downregulation of ceramide-generating enzymes. However, chemotherapeutic drugs as well as radiotherapy increase intracellular ceramide levels, while exogenously treating cancer cells with short-chain ceramides leads to anticancer effects. All evidence currently points to the fact that the upregulation of ceramide levels is a promising anticancer strategy. In this review, we exhibit many anticancer ceramide analogs as downstream receptor agonists and ceramide-metabolizing enzyme inhibitors.

Figures

Figure 1
Figure 1
Ceramide metabolism and signaling pathways and their anti-cancer targets. Cer, ceramide; CDase, ceramidase; Sph, sphingosine; SK, sphingosine kinase; S1P, sphingosine-1-phosphate; CerK, ceramide kinase; C1P, ceramide-1-phosphate; SMS, sphingomyelin synthase; SM, sphingomyelin; GCS, glucosylceramide synthase; GluCer, glucosylceramide; SMase, sphingomyelinase; ASK1, Apoptosis signal-regulating kinase 1; JNK, c-Jun N-terminal kinase; BAX, BCL-2–associated X protein; PP2A, protein phosphatase 2A; AKT, serine/threonine-specific protein kinase; BCL-2, B-cell lymphoma 2; ERK, extracellular-signal-regulated kinase; ABC transporter, ATP-binding cassette transporter.
Figure 2
Figure 2
Structures of the naturally occurring ceramide, D-erythro-C18-ceramide (C18-Cer), and synthetic short-chain ceramides, C2-Cer, C6-Cer, and C8-Cer
Figure 3
Figure 3
Structures of the four stereoisomers of C2-Cer and the four stereoisomers of C2-dhCer studied by [56]
Figure 4
Figure 4
The B13-family of ceramide analogs
Figure 5
Figure 5
Evolution of PDMP-family ceramide analogs (targeting glucosylceramide synthase, GCS)
Figure 6
Figure 6
Sphingosine-derivative sphingosine kinase inhibitors

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