Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

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Ceramide in Apoptotic Signaling and Anticancer Therapy

Author(s): C. F. Lin, C. L. Chen and Y. S. Lin

Affiliation: Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan 701, Taiwan.

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

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Article Details

VOLUME: 13
ISSUE: 14
Page: [1609 - 1616]
Pages: 8
DOI: 10.2174/092986706777441986
Price: $58