Research Publications - College of Medicine and Health Science

Department of Biochemistry
Doxorubicin induces
ceramide generation
and apoptosis in human
leukemic cells. Jurkat,
Molt-4 and K562 cells
were treated with
indicated concentrations
of doxorubicin, (A)
measurement of
ceramide generation
and (B) analysis of DNA
fragmentation (top
panel) and PARP cleavage
(Bottom panel).
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sine is phosphorylated to form S1P through the
action of sphingosine kinase. Because the phosphorylation
of sphingosine is the only pathway
for the formation of S1P and cellular S1P is
highly dependent on the availability of sphingosine
generated by ceramidases, suggesting
that ceramidases are critical in regulating not
only the hydrolysis of ceramide but also the
generation of both sphingosine and S1P in cells.
Therefore, the action of ceramidase leads to
an alteration in cellular ceramide, sphingosine,
and S1P, thereby controlling cellular responses
mediated by these bioactive lipids.
Ceramide mediates the regulation of growth
arrest, senescence, and/or apoptosis. Some of
these biological functions might be controlled
through novel sphingolipid-protein interactions.
Frequently, these targets of ceramide
constitute protein phosphatases and kinases
that regulate important signaling pathways in
cancer, such as Akt, protein kinase C (PKC), MAP
kinases, or phospholipase D.
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stress stimuli.
Ceramide production is enhanced in response
to environmental stress, ionic/ultraviolet radiation,
heat, hypoxia, reperfusion, cytokines and
growth factors, tumor necrosis factors, interferon-gamma,
and interlekin-1-beta as well as
chemotherapeutic agents, doxorubicin, adriamycin,
tamoxifen, paclitaxel, 4-HRP and phytochemicals
such as curcumin and capsaicin.