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Role of ceramide in suramin-induced cancer cell death
1Molecular Neuroscience Program and Mayo Cancer Center, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. gill.jag@mayo.edu
Abstract:
Suramin is an experimental antineoplastic agent which is currently being tested in clinical trials for its utility in treating breast and prostate cancer. Recent in vitro studies from our laboratory report a disruption in glycolipid metabolism and cell death in suramin-treated neurons. Evidence presented in this study proposes to consolidate the neurotoxic and cytotoxic effects of suramin. Electron microscopic studies, bis-benzimide staining and DNA gel electrophoresis of suramin and C2-ceramide treatment revealed apoptotic cells in human breast, prostate and rat neuron like cell lines. Apoptotic cell death was preceded by an elevation in intracellular ceramide.
Insights
Suramin, an experimental cancer drug, causes cell death in neurons and cancer cells by disrupting lipid metabolism and increasing ceramide levels. This study confirms its neurotoxic and cytotoxic effects, impacting breast, prostate, and neuronal cell lines.
Area of Science:
- Oncology
- Neuroscience
- Cell Biology
Background:
- Suramin is an experimental antineoplastic agent undergoing clinical trials for breast and prostate cancer.
- Previous in vitro studies indicated suramin disrupts glycolipid metabolism and induces cell death in neurons.
Purpose of the Study:
- To consolidate the neurotoxic and cytotoxic effects of suramin.
- To investigate the role of ceramide in suramin-induced cell death.
Main Methods:
- Electron microscopy
- Bis-benzimide staining
- DNA gel electrophoresis
- Treatment of human breast, prostate, and rat neuron-like cell lines with suramin and C2-ceramide.
Main Results:
- Apoptotic cell death was observed in human breast, prostate, and rat neuron-like cell lines following suramin and C2-ceramide treatment.
- An elevation in intracellular ceramide preceded the induction of apoptotic cell death.
Conclusions:
- Suramin exhibits both neurotoxic and cytotoxic effects.
- Increased intracellular ceramide is implicated in the mechanism of suramin-induced apoptosis in cancer and neuronal cells.