title: Sulindac sulfide--induced stimulation of eryptosis.
abstract: BACKGROUND
  Sulindac sulfide, a non-steroidal anti-inflammatory drug (NSAID), stimulates apoptosis of tumor cells and is thus effective against malignancy. In analogy to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, an apoptosis-like suicidal erythrocyte death, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine-exposure at the cell surface. Stimulators of eryptosis include increase of cytosolic Ca(2+)-activity ([Ca(2+)](i)) and ceramide formation. The present study explored, whether sulindac sulfide stimulates eryptosis.
  
  
  METHODS
  [Ca(2+)](i) was estimated from Fluo-3 fluorescence, cell volume from forward scatter, phosphatidylserine-exposure from binding of fluorescent annexin-V, hemolysis from hemoglobin release, and ceramide abundance utilizing fluorescent antibodies.
  
  
  RESULTS
  A 48 h exposure to sulindac sulfide (≤ 20 µM) was followed by significant increase of [Ca(2+)](i), enhanced ceramide abundance, decreased forward scatter and increased percentage of annexin-V-binding erythrocytes. Sulindac sulfide triggered slight but significant hemolysis. Removal of extracellular Ca(2+) significantly blunted, but did not abrogate the effect of sulindac sulfide (20 µM) on annexin-V-binding.
  
  
  CONCLUSIONS
  Sulindac sulfide stimulates the suicidal death of erythrocytes or eryptosis, an effect paralleled by Ca(2+)-entry, ceramide formation, cell shrinkage and phosphatidylserine-exposure.
authors.affiliation: Department of Physiology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Mohanad
authors.initials: M
authors.lastname: Zbidah
authors.forename: Adrian
authors.initials: A
authors.lastname: Lupescu
authors.forename: Wenting
authors.initials: W
authors.lastname: Yang
authors.forename: Anastasia
authors.initials: A
authors.lastname: Bosc
authors.forename: Kashif
authors.initials: K
authors.lastname: Jilani
authors.forename: Nazneen
authors.initials: N
authors.lastname: Shaik
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000814:Aniline Compounds / Q000032:analysis; D017304:Annexin A5 / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000032:analysis; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology; D014966:Xanthenes / Q000032:analysis
chemical_list: D000814:Aniline Compounds; D017304:Annexin A5; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D002518:Ceramides; D005456:Fluorescent Dyes; D010718:Phosphatidylserines; D014966:Xanthenes; D013467:Sulindac; C059715:Fluo-3; C025462:sulindac sulfide; D002118:Calcium