Role of ceramide in suramin-induced cancer cell death.
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.
Gill
J S
JS
Molecular Neuroscience Program and Mayo Cancer Center, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. gill.jag@mayo.edu
Windebank
A J
AJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000493:pharmacokinetics / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D010673:Pheochromocytoma / Q000648:ultrastructure; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002518:Ceramides; D013498:Suramin