Bcl-2 antagonizes apoptotic cell death induced by two new ceramide analogues

FEBS Lett. 1997 Jul 14;411(2-3):260-4. doi: 10.1016/s0014-5793(97)00717-5.

Abstract

Ceramides which arise in part from the breakdown of sphingomyelin comprise a class of antiproliferative lipids and have been implicated in the regulation of programmed cell death better known as apoptosis. In the present study, two new synthetic ceramide analogues, N-thioacetylsphingosine and FS-5, were used in Molt 4 cells to induce cell death. Besides their cytotoxic effects at concentrations > or = 14 microM the data obtained clearly show that both analogues induced apoptosis at concentrations below this critical concentration as assessed by trypan blue exclusion and cleavage of the death substrate poly-(ADP-ribose) polymerase (PARP). Additional experiments in bcl-2-transfected Molt 4 cells revealed that the apoptotic but not the lytic effects of the analogues were antagonized by the apoptosis inhibitor Bcl-2. Furthermore, neither N-thio-acetylsphingosine nor FS-5 induced PARP cleavage in bcl-2-transfected Molt 4 cells indicating that the induction of apoptotic cell death by cell permeable ceramides is not due to unspecific disturbance of the cell membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Survival / drug effects
  • Ceramides / analysis
  • Ceramides / chemical synthesis
  • Ceramides / pharmacology*
  • Etoposide / pharmacology
  • Genes, bcl-2*
  • Humans
  • Molecular Structure
  • Poly(ADP-ribose) Polymerases / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / chemical synthesis
  • Sphingosine / pharmacology
  • Transfection
  • Trypan Blue / metabolism
  • Tumor Cells, Cultured

Substances

  • 4-(dodecanoylamino)decan-5-ol
  • Amides
  • Antineoplastic Agents, Phytogenic
  • Ceramides
  • N-acetylsphingosine
  • N-thioacetylsphingosine
  • Etoposide
  • Poly(ADP-ribose) Polymerases
  • Trypan Blue
  • Sphingosine