Journal
EUROPEAN JOURNAL OF BIOCHEMISTRY
Volume 268, Issue 2, Pages 193-204Publisher
WILEY
DOI: 10.1046/j.1432-1033.2001.01845.x
Keywords
apoptosis; cancer chemotherapy; ceramide concentration; ceramide metabolism; glucosylceramide synthesis inhibition; hormone effects on ceramide; multidrug resistance; sphingomyelin-ceramide pathway
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Many papers have shown that sphingolipids control the balance in cells between growth and proliferation, and cell death by apoptosis. Sphingosine-1-phosphate (Sph1P) 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-Sph1P 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.
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