Suramin induced ceramide accumulation leads to apoptotic cell death in dorsal root ganglion neurons

Jagjit S. Gill, Anthony J. Windebank

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Suramin is an experimental antineoplastic agent that is currently being tested in clinical trials for a number of human cancers. In previous clinical trials, it has been noted that a significant percentage of patients treated with suramin develop a peripheral neuropathy. Both the cytotoxic (chemotherapeutic) and neurotoxic mechanisms of action of this compound are unknown. Evidence presented in this study suggests that both effects may be due to extensive disruption in glycolipid transport and/or metabolism. Suramin treated dorsal root ganglion cultures revealed an accumulation of the GM1 ganglioside and ceramide. Exposure of cultures to suramin, a cell permeable ceramide analog, or sphingomyelinase lead to apoptotic cell death demonstrated by electron microscopy, bis-benzimide staining and DNA laddering on gel electrophoresis. Furthermore, a significant increase in intracellular ceramide preceded cell death in suramin treated neurons. We propose that suramin induced ceramide accumulation within neurons leads to apoptotic cell death.

Original languageEnglish (US)
Pages (from-to)876-883
Number of pages8
JournalCell Death and Differentiation
Volume5
Issue number10
DOIs
StatePublished - Oct 1998

Keywords

  • Apoptosis
  • Ceramide
  • Chemotherapy
  • Dorsal root ganglion
  • Peripheral neuropathy

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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