Enzymes of sphingosine metabolism as potential pharmacological targets for therapeutic intervention in cancer.
Whereas some sphingolipids such as sphingoid bases and ceramide can mediate and induce cell killing, other sphingolipids such as sphingosine 1-phosphate promote cell survival or proliferation. The tight equilibrium between the intracellular levels of each of these biomodulators is controlled by the various enzymes that either produce or degrade these lipid molecules. Herein, the effects of sphingoid bases and their derivatives on the regulation of (cancer) cell growth and death are reviewed. In addition, the consequences of pharmacological manipulation of the enzymes that govern sphingoid base metabolism on in vitro and in vivo tumor cell growth are presented. Further development of pharmacological tools aimed at interfering with the metabolism of sphingolipids is expected to provide new avenues in the treatment of cancers as well as other diseases.
Cuvillier
Olivier
O
Inserm U466, Hôpital Rangueil, TSA 50032, 1 Avenue Jean Poulhès, 31059 Toulouse Cedex 9, France. olivier.cuvillier@toulouse.inserm.fr
Levade
Thierry
T
D000818:Animals; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D013107:Sphingolipids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013110:Sphingosine / Q000037:antagonists & inhibitors / Q000378:metabolism*
D013107:Sphingolipids; D013110:Sphingosine