title: Triggering of Suicidal Erythrocyte Death by Topotecan.
abstract: OBJECTIVE
  The topoisomerase I inhibitor topotecan is used as treatment of various malignancies. The substance is effective by triggering tumor cell apoptosis. In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the outer face of the erythrocyte membrane. Signaling leading to eryptosis include Ca(2+)-entry and ceramide formation. The present study explored, whether and how topotecan induces eryptosis.
  
  
  METHODS
  Phosphatidylserine abundance at the erythrocyte surface was estimated from annexin V binding, cell volume from forward scatter, and ceramide abundance utilizing specific antibodies.
  
  
  RESULTS
  A 48 hours exposure of human erythrocytes to topotecan significantly increased the percentage of annexin-V-binding cells and significantly decreased forward scatter. The effect of topotecan was paralleled by a significant increase of ceramide abundance. The effect of topotecan on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+.
  
  
  CONCLUSIONS
  Topotecan stimulated cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect paralleled by increase of ceramide abundance and partially dependent on entry of extracellular Ca2+.
authors.forename: Rosi
authors.initials: R
authors.lastname: Bissinger
authors.forename: Ghada
authors.initials: G
authors.lastname: Bouguerra
authors.forename: Katja
authors.initials: K
authors.lastname: Stockinger
authors.forename: Salem
authors.initials: S
authors.lastname: Abbès
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology; D019772:Topotecan / Q000494:pharmacology*
chemical_list: D002518:Ceramides; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D059004:Topoisomerase I Inhibitors; D019772:Topotecan; D002118:Calcium