Ceramidases in Hematological Malignancies: Senseless or Neglected Target?

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
France


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Ceramidases in Hematological Malignancies: Senseless or Neglected Target?



Anti-Cancer Agents in Medicinal Chemistry, 11(9): 830-843.

Author(s): Gemma Fabrias, Carmen Bedia, Josefina Casas, Jose Luis Abad and Antonio Delgado.

Affiliation: Spanish National Research Council (Consejo Superior de Investigaciones Cientificas, CSIC), Research Unit on Bioactive Molecules (RUBAM); Departament de Quimica Biomedica; Institut de Quimica Avancada de Catalunya (IQAC); Jordi Girona 18-26, 08034 Barcelona, Spain.

Abstract

Ceramidases are ubiquitous amidohydrolases that catalyze the cleavage of ceramides into sphingosine and fatty acids. This reaction exerts a cytoprotective role in physiological conditions, while altered ceramidase activities favour a number of human diseases. Among these diseases, several reports point to important roles of ceramidases, mainly the acid ceramidase, in the initiation and progression of cancer, and the response of tumors to radio- or chemotherapy. Multiple reports confirm the interest of acid ceramidase inhibitors as anticancer drugs, either alone or in combination with other therapies. Sphingolipid metabolism plays a role in hematological malignancies and appears as an interesting target for therapeutic intervention. Although the use of ceramidase inhibitors in chemotherapy of hematologic cancers has not been widely investigated, a number of indirect evidence suggest that inhibition of specific ceramidases could potentiate the effect of drugs in clinical use to treat hematologic malignancies and may afford strategies to combat relapses. The arsenal of ceramidase inhibitors so far available is wide and hopefully, upcoming research will assess the feasibility of this approach.

Keywords:

Sphingolipids, ceramidase, cancer, enzyme inhibitor, chemotherapy, enzyme assay, ACERs, AC, NC, ER, NOE, LNCaP.



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Article Details

Volume: 11
Issue Number: 9
First Page: 830
Last Page: 843
Page Count: 14
DOI: 10.2174/187152011797655104
Price: $58
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