Resistance to CD95/Fas-induced and ceramide-mediated apoptosis of human melanoma cells is caused by a defective mitochondrial cytochrome c release

Raisova M., BEKTAŞ M., Wieder T., Daniel P., Eberle J., Orfanos C., ...More

FEBS LETTERS, vol.473, no.1, pp.27-32, 2000 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 473 Issue: 1
  • Publication Date: 2000
  • Doi Number: 10.1016/s0014-5793(00)01491-5
  • Journal Name: FEBS LETTERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.27-32
  • Keywords: 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
  • Istanbul University Affiliated: No

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 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.