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  • Title: Resistance to CD95/Fas-induced and ceramide-mediated apoptosis of human melanoma cells is caused by a defective mitochondrial cytochrome c release.
    Author: Raisova M, Bektas M, Wieder T, Daniel P, Eberle J, Orfanos CE, Geilen CC.
    Journal: FEBS Lett; 2000 May 04; 473(1):27-32. PubMed ID: 10802053.
    Abstract:
    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.
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