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Resistance to CD95/Fas‐induced and ceramide‐mediated apoptosis of human melanoma cells is caused by a defective mitochondrial cytochrome c release
Author(s) -
Raisova Monika,
Bektas Meryem,
Wieder Thomas,
Daniel Peter,
Eberle Jürgen,
Orfanos Constantin E.,
Geilen Christoph C.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01491-5
Subject(s) - apoptosis , cytochrome c , fas receptor , ceramide , microbiology and biotechnology , dna fragmentation , mitochondrion , uvb induced apoptosis , programmed cell death , caspase 8 , fas ligand , caspase , chemistry , intracellular , biology , biochemistry
Intracellular CD95/Fas‐signaling pathways have not been investigated in melanoma yet. Two different CD95 receptor‐induced apoptotic pathways are presently known in other cell types: (i) direct activation of caspase‐8 and (ii) induction of ceramide‐mediated mitochondrial activation, both leading to subsequent caspase‐3 activation. In the present study, five of 11 melanoma cell populations were shown to release cytochrome c from mitochondria, which activates caspase‐3 and finally results in DNA fragmentation upon treatment with the agonistic monoclonal antibody CH‐11. In contrast, this apoptotic pathway was not activated in the remaining six melanoma cell populations. Interestingly, the susceptibility of melanoma cells to CD95L/FasL‐triggered cell death was clearly correlated with N ‐acetylsphingosine‐mediated apoptosis. Our results are in line with a defect upstream of mitochondrial cytochrome c release in resistant cells.