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 language | English (US) |
|---|---|
| Pages (from-to) | 876-883 |
| Number of pages | 8 |
| Journal | Cell Death and Differentiation |
| Volume | 5 |
| Issue number | 10 |
| State | Published - Oct 1998 |
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Keywords
- Apoptosis
- Ceramide
- Chemotherapy
- Dorsal root ganglion
- Peripheral neuropathy
ASJC Scopus subject areas
- Cell Biology
Cite this
Suramin induced ceramide accumulation leads to apoptotic cell death in dorsal root ganglion neurons. / Gill, Jagjit S.; Windebank, Anthony John.
In: Cell Death and Differentiation, Vol. 5, No. 10, 10.1998, p. 876-883.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suramin induced ceramide accumulation leads to apoptotic cell death in dorsal root ganglion neurons
AU - Gill, Jagjit S.
AU - Windebank, Anthony John
PY - 1998/10
Y1 - 1998/10
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Ceramide
KW - Chemotherapy
KW - Dorsal root ganglion
KW - Peripheral neuropathy
UR - http://www.scopus.com/inward/record.url?scp=0031788607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031788607&partnerID=8YFLogxK
M3 - Article
C2 - 10203686
AN - SCOPUS:0031788607
VL - 5
SP - 876
EP - 883
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
IS - 10
ER -