Open AccessKilling cancer cells by poly‐drug elevation of ceramide levels
Author(s) -
Radin Norman S.
Publication year - 2001
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1033.2001.01845.x
Subject(s) - ceramide , sphingolipid , sphingosine , apoptosis , sphingosine 1 phosphate , cancer cell , ceramide synthase , programmed cell death , microbiology and biotechnology , lipid signaling , cancer , biology , drug , cancer research , cell growth , enzyme , pharmacology , biochemistry , receptor , genetics
Many papers have shown that sphingolipids control the balance in cells between growth and proliferation, and cell death by apoptosis. Sphingosine‐1‐phosphate (Sph1 P ) and glucosylceramide (GlcCer) induce proliferation processes, and ceramide (Cer), a metabolic intermediate between the two, induces apoptosis. In cancers, the balance seems to have come undone and it should be possible to kill the cells by enhancing the processes that lead to ceramide accumulation. The two control systems are intertwined, modulated by a variety of agents affecting the activities of the enzymes in Cer‐GlcCer‐Sph1 P interdependence. It is proposed that successful cancer chemotherapy requires the use of many agents to elevate ceramide levels adequately. This review updates current knowledge of sphingolipid metabolism and some of the evidence showing that ceramide plays a causal role in apoptosis induction, as well as a chemotherapeutic agent.