The role of ceramide in the cellular response to cytotoxic agents.
The sphingolipid messenger ceramide has been implicated in the initiation of apoptotic cell death in a variety of physiologic settings. Recent investigation has shown that ceramide-dependent stress signaling is associated with chemotherapy-related apoptosis. It is not entirely clear, however, whether drug-mediated generation of ceramide is essential for execution of the cell death program, or simply represents a component of the genotoxic stress response. For example, there is evidence that ceramide subserves an important role in certain stresses (e.g., ionizing radiation, daunorubicin) but represents a secondary process in others (e.g., cytarabine). The review presents evidence for and against a cytotoxic effector function for ceramide in the lethal actions of conventional antineoplastic agents.
Jarvis
W D
WD
Department of Medicine, Medical College of Virginia, Richmond 23298-0230, USA.
Grant
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S
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002518:Ceramides / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D019014:fas Receptor / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D002518:Ceramides; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor