Molecular targeting of acid ceramidase: implications to cancer therapy.
Increasingly recognized as bioactive molecules, sphingolipids have been studied in a variety of disease models. The impact of sphingolipids on cancer research facilitated the entry of sphingolipid analogues and enzyme modulators into clinical trials. Owing to its ability to regulate two bioactive sphingolipids, ceramide and sphingosine-1-phosphate, acid ceramidase (AC) emerges as an attractive target for drug development within the sphingolipid metabolic pathway. Indeed, there is extensive evidence supporting a pivotal role for AC in lipid metabolism and cancer biology. In this article, we review the current knowledge of the biochemical properties of AC, its relevance to tumor promotion, and its molecular targeting approaches.
Zeidan
Youssef H
YH
Department of Biochemistry and Molecular Biology Medical University of South Carolina .175 Ashley Avenue, P.O. Box 250509. Charleston, South Carolina, 29425, USA.
Jenkins
Russell W
RW
Korman
John B
JB
Liu
Xiang
X
Obeid
Lina M
LM
Norris
James S
JS
Hannun
Yusuf A
YA
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002518:Ceramides / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D002517:Galactosylgalactosylglucosylceramidase / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008246:Lysophospholipids / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
D000970:Antineoplastic Agents; D002518:Ceramides; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D002517:Galactosylgalactosylglucosylceramidase; D013110:Sphingosine