Resistance to CD95/Fas-induced and ceramide-mediated apoptosis of human melanoma cells is caused by a defective mitochondrial cytochrome c release
FEBS LETTERS, cilt.473, sa.1, ss.27-32, 2000 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 473 Sayı: 1
- Basım Tarihi: 2000
- Doi Numarası: 10.1016/s0014-5793(00)01491-5
- Dergi Adı: FEBS LETTERS
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.27-32
- Anahtar Kelimeler: CD95/Fas, signaling, mitochondrion, melanoma, cytochrome c release, HUMAN-MALIGNANT-MELANOMA, SPHINGOMYELIN HYDROLYSIS, HUMAN MELANOCYTES, SURFACE-ANTIGENS, TUMOR-CELLS, BAX-ALPHA, BCL-2, FAS, EXPRESSION, DEATH
- İstanbul Üniversitesi Adresli: Hayır
Özet
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 II 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. (C) 2000 Federation of European Biochemical Societies.