Ceramide increases Fas-mediated apoptosis in glioblastoma cells through FLIP down-regulation.
Ceramide is a physiologic regulator of growth and differentiation in mammalian cells. In this study, the relationship between ceramide and FLICE inhibitory protein (FLIP) in the induction of apoptosis in glioblastoma cell lines was investigated. We found that LN215 cells were slightly more sensitive to Fas-mediated apoptosis than LN319 cells, which were more sensitive to ceramide than LN215 cells. FLIP was expressed in LN319 and LN215 cells constitutively, and this expression decreased with treatment of ceramide in LN215 cells, which might cause LN215 cells to be more sensitive to Fas-mediated apoptosis at lower level stimulation. In LN319 cells FLIP levels were not modified by ceramide treatment and the level of cell death induced by anti-Fas antibody was not affected. Our results suggest that FLIP may be down-regulated by low levels of ceramide in LN215 cells, which causes LN215 cells to be more sensitive to Fas-mediated apoptosis, whereas LN319 cells remain resistant.
Yoon
Gitae
G
Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Kim
Kyoung-Ok
KO
Lee
Jeonggi
J
Kwon
Daeho
D
Shin
Jeon-Soo
JS
Kim
Se-Jong
SJ
Choi
In-Hong
IH
D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000378:metabolism*; D002518:Ceramides / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D005909:Glioblastoma; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D002518:Ceramides; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor