Sphingolipids in anticancer therapy.
Sphingolipids constitute a broad class of compounds with many biological functions. The sphingolipid metabolites ceramide and sphingosine are potent apoptosis inducers and produce cell cycle arrest, whereas sphingosine-1-phosphate promotes cellular growth and differentiation. Herein, the effects of sphingolipids and their analogs on diverse signaling pathways implicated in the apoptotic process are highlighted. The relatively simple chemical structure of these compounds has led to several strategies for their total synthesis. Those methods have contributed to the development and biological study of several analogs that present diverse degree of modification from the original structure. This article catalogues many of the recently developed synthetic analogs that act on diverse aspects of sphingolipid metabolism. A description of known enzyme inhibitors of the sphigolipids pathway is also given. Finally, diverse new sphingolipid-like antitumor agents isolated from marine sources are presented. This contribution opens the way for future development of new sphingolipid analogs that might be useful in cancer chemotherapy.
Padrón
José M
JM
Instituto Canario de Investigación del Cáncer (ICIC), Red Temática de Investigación Cooperativa de Centros de Cáncer (RTICCC), Ctra. del Rosario s/n, 38010 S/C de Tenerife, Spain. jmpadron@ull.es
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013107:Sphingolipids / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013107:Sphingolipids