Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 16, 12 Issues, 2016

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex

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Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias

Anti-Cancer Agents in Medicinal Chemistry, 11(4): 385-397.

Author(s): Huseyin Atakan Ekiz and Yusuf Baran.

Affiliation: Izmir Institute of Technology,Department of Molecular Biology and Genetics; Urla/Izmir/Turkey.


Sphingolipids are major constituents of the cells with emerging roles in the regulation of cellular processes. Deregulation of sphingolipid metabolism is reflected as various pathophysiological conditions including metabolic disorders and several forms of cancer. Ceramides, ceramide-1-phosphate (C1P), glucosyl ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P) are among the bioactive sphingolipid species that have important roles in the regulation of cell death, survival and chemotherapeutic resistance. Some of those species are known to accumulate in the cells upon chemotherapy while some others are known to exhibit an opposite pattern. Even though the length of fatty acid chain has a deterministic effect, in general, upregulation of ceramides and sphingosine is known to induce apoptosis. However, S1P, C1P and GluCer are proliferative for cells and they are involved in the development of chemoresistance. Therefore, sphingolipid metabolism appears as a good target for the development of novel therapeutics or supportive interventions to increase the effectiveness of the chemotherapeutic drugs currently in hand. Some approaches involve manipulation of the synthesis pathways yielding the increased production of apoptotic sphingolipids while the proliferative ones are suppressed. Some others are trying to take advantage of cytotoxic sphingolipids like short chain ceramide analogs by directly delivering them to the malignant cells as a distinct chemotherapeutic intervention. Numerous studies in the literature show the feasibility of those approaches especially in acute and chronic leukemias. This review compiles the current knowledge about sphingolipids and their roles in chemotherapeutic response with the particular attention to leukemias.


Ceramide, ceramide-1-phosphate, chemotherapeutic response, dihydroceramide, glucosylceramide, leukemia, sphingosine, sphingosine-1-phosphate, glucosylceramide (GluCer), dihydroceramide (dhCer), sphingosine (Sph), sphingosine-1-phosphate (S1P), 3-ketosphinganine, sphingomyelin synthase, pathophysiological conditions.

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Article Details

Volume: 11
Issue Number: 4
First Page: 385
Last Page: 397
Page Count: 13
DOI: 10.2174/187152011795677571
Price: $58

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