[Molecular targeting therapy for leukemia by sphingolipid ceramide].
Ceramide has been recognized as a structural component to consist of the cell membrane. Since we reported that ceramide content increased in vitamin-D3-induced cell differentiation of human leukemia HL-60 cells, it has become evident that ceramide acts as an intracellular lipid mediator to transduce an extracellular stress into the cells. Ceramide is synthesized through serine-palmitoyl CoA transferase. Diversity of ceramide species derives from the changes of carbon length of fatty acid binding to amine part of sphingosine. A variety of stresses induce apoptosis through activation of pro-apoptotic signals as well as inhibition of antiapoptotic/survival signals by an increase of intracellular ceramide. Here, the recent problems and innovation in the medication of hematological malignancy are summarized, and it is suggested that the induction of apoptotic cell death by ceramide action is a potent, novel molecular targeting therapy for a chemoresistant and refractory hematological malignancy.
Okazaki
Toshiro
T
Division of Clinical Laboratory Medicine/Hematology, Tottori University Faculty of Medicine, Yonago 683-8504.
D017209:Apoptosis; D002518:Ceramides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005964:Glucosyltransferases / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D013107:Sphingolipids
D002518:Ceramides; D013107:Sphingolipids; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase