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Review
. 2019 Jul;26(4):407-415.
doi: 10.1007/s12282-019-00953-8. Epub 2019 Apr 8.

Clinical application of ceramide in cancer treatment

Kazuki Moro  1 , Masayuki Nagahashi  2 , Emmanuel Gabriel  3 , Kazuaki Takabe  1   4   5 , Toshifumi Wakai  1
Affiliations
Review

Clinical application of ceramide in cancer treatment

Kazuki Moro et al. Breast Cancer. 2019 Jul.

Abstract

Development of innovative strategies for cancer treatment is a pressing public health issue. Despite recent advances, the mechanisms of cancer progression and the resistance to cancer treatment have not been fully elucidated. Sphingolipids, including ceramide and sphingoshin-1-phosphate, are bioactive mediators that regulate cancer cell death and survival through the dynamic balance of what has been termed the 'sphingolipid rheostat'. Specifically, ceramide, which acts as the central hub of sphingolipid metabolism, is generated via three major pathways by many stressors, including anti-cancer treatments, environmental stresses, and cytokines. We have previously shown in breast cancer patients that elevated ceramide correlated with less aggressive cancer phenotypes, leading to a prognostic impact. Recent studies showed that ceramide have the possibility of becoming the reinforcing agent of cancer treatment as well as other roles such as nanoparticles and diagnostic biomarker. We review ceramide as one of the key molecules to investigate in overcoming resistance to current drug therapies and in becoming one of the newest cancer treatments.

Keywords: Apoptosis; Cancer; Ceramide; Drug resistance; Sphingosine-1-phosphate.

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Conflict of interest statement

Conflict of Interest Statement

The authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
The sphingolipid rheostat. The schema shows the important enzymes and organelles that regulate the levels of ceramide and sphingosine-1-phosphate (S1P). ABC, ATP-binding cassette; CDase, ceramidase; Cer, ceramide; CerS, ceramide synthases; ER, endoplasmic reticulum; SphK, sphingosine kinase; Spns2, Spinster homologue 2; SPP, S1P phosphatase; S1PR, S1P receptor.
Fig. 2
Fig. 2
Pathways for ceramide metabolism. Ceramide synthesis has three main metabolic pathways; the de novo pathway, the salvage pathway, and sphingomyelin pathway. Ceramide is metabolized to ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P) through catabolic pathways. CDase, ceramidase; CerS, ceramide synthases; DES1, dihydroceramide desaturase 1; GBA, glucocerebrosidase; GCS, glucosylceramide synthase; SM, sphingomyelin; SphK, sphingosine kinase; SPP, S1P phosphatase.
See this image and copyright information in PMC

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