TY - JOUR
T1 - Ceramide in apoptotic signaling and anticancer therapy
AU - Lin, C. F.
AU - Chen, Chia-Ling
AU - Lin, Yee-Shin
PY - 2006/6
Y1 - 2006/6
N2 - 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. P13K/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.
AB - 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. P13K/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.
KW - Anticancer
KW - Apoptosis
KW - Caspase
KW - Ceramide
KW - Mitochondria
KW - Protein kinase
KW - Protein phosphatase
KW - Sphingolipid
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U2 - 10.2174/092986706777441986
DO - 10.2174/092986706777441986
M3 - Article
C2 - 16787207
AN - SCOPUS:33744749249
VL - 13
SP - 1609
EP - 1616
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
SN - 0929-8673
IS - 14
ER -