CD95 ligand-induced apoptosis of human medulloblastoma cells

Cancer Lett. 1998 Jun 19;128(2):121-6. doi: 10.1016/s0304-3835(98)00019-6.

Abstract

CD95 ligand (CD95L) is a cytotoxic cytokine that induces apoptosis in susceptible target cells. Medulloblastoma is the most common non-glial intrinsic malignancy of the brain. In this study, we have studied CD95-mediated apoptosis of human medulloblastoma cell lines. We found that DAOY, MED-1 and D-283 cells are susceptible to CD95L-induced apoptosis when RNA and protein synthesis are inhibited. Preexposure of D-283, but not DAOY or MED-1 cells, to interferon-gamma or tumor necrosis factor-alpha enhances CD95 expression and primes these cells for CD95-mediated apoptosis. Inhibitors of interleukin 1-converting enzyme (ICE)-like protease (caspase) activity block CD95L-induced cytotoxicity, suggesting that caspases mediate the death signal induced by CD95L in human medulloblastoma cells. Interestingly, medulloblastoma cells belong to an increasing number of tumor cell types that coexpress CD95 and CD95L. We conclude that CD95 may be a promising target of immunochemotherapy for human medulloblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / physiology*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Fas Ligand Protein
  • Humans
  • Interferon-gamma / pharmacology
  • Medulloblastoma / drug therapy
  • Medulloblastoma / metabolism
  • Medulloblastoma / pathology*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Neoplasm Proteins / biosynthesis
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Suppressor Protein p53 / biosynthesis
  • bcl-2-Associated X Protein

Substances

  • Antineoplastic Agents
  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Neoplasm
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Interferon-gamma