Abstract
Ceramide, a product of sphingolipid metabolism, is generated in response to various stress stimuli, such as tumor necrosis factor-α, CD95/Fas, chemotherapeutic agents, and irradiation. Ceramide may modulate the biochemical and cellular processes that lead to apoptosis. However, the mechanisms by which ceramide regulates apoptotic events are not fully defined. It is believed that the biological effect of ceramide depends on its concentration, the activation or differentiation status of the cell, and the time frame of action. Here, we discuss the metabolism and cell apoptotic signaling of ceramide. The involvement of protein kinases (i.e. PI3K/Akt and GSK-3β) and protein phosphatases (i.e. PP1 and PP2A), Bcl-2 family proteins, mitochondrial damage, and caspase cascade activation are demonstrated. Further, ceramide and its derivatives have recently been incorporated into strategies for anticancer therapies. An understanding of the apoptotic signaling pathways mediated by ceramide may shed light on its potential for therapeutic intervention.
Keywords: ceramide, sphingolipid, apoptosis, protein kinase, protein phosphatase, mitochondria, caspase, anticancer
Current Medicinal Chemistry
Title: Ceramide in Apoptotic Signaling and Anticancer Therapy
Volume: 13 Issue: 14
Author(s): C. F. Lin, C. L. Chen and Y. S. Lin
Affiliation:
Keywords: ceramide, sphingolipid, apoptosis, protein kinase, protein phosphatase, mitochondria, caspase, anticancer
Abstract: Ceramide, a product of sphingolipid metabolism, is generated in response to various stress stimuli, such as tumor necrosis factor-α, CD95/Fas, chemotherapeutic agents, and irradiation. Ceramide may modulate the biochemical and cellular processes that lead to apoptosis. However, the mechanisms by which ceramide regulates apoptotic events are not fully defined. It is believed that the biological effect of ceramide depends on its concentration, the activation or differentiation status of the cell, and the time frame of action. Here, we discuss the metabolism and cell apoptotic signaling of ceramide. The involvement of protein kinases (i.e. PI3K/Akt and GSK-3β) and protein phosphatases (i.e. PP1 and PP2A), Bcl-2 family proteins, mitochondrial damage, and caspase cascade activation are demonstrated. Further, ceramide and its derivatives have recently been incorporated into strategies for anticancer therapies. An understanding of the apoptotic signaling pathways mediated by ceramide may shed light on its potential for therapeutic intervention.
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Cite this article as:
Lin F. C., Chen L. C. and Lin S. Y., Ceramide in Apoptotic Signaling and Anticancer Therapy, Current Medicinal Chemistry 2006; 13 (14) . https://dx.doi.org/10.2174/092986706777441986
DOI https://dx.doi.org/10.2174/092986706777441986 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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