title: Enhanced eryptosis following auranofin exposure.
abstract: OBJECTIVE
  The antiinflammatory, antimicrobial and anticancer drug auranofin has previously been shown to trigger apoptosis, the suicidal death of nucleated cells. Side effects of the drug include anaemia. At least in theory the anaemia could result from stimulation of suicidal death of erythrocytes or eryptosis, which involves cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface.
  
  
  METHODS
  Stimulators of eryptosis include oxidative stress and increase of cytosolic Ca2+-activity ([Ca2+]i). In the present study, phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, and [Ca2+]i from Fluo3-fluorescence.
  
  
  RESULTS
  A 24 hours exposure of human erythrocytes to auranofin (≥5 µg/ml) significantly increased the percentage of annexin-V-binding cells (from 2.2 ± 0.5 to 17.4 ± 1.5%), significantly decreased forward scatter and significantly enhanced ROS. At higher concentrations (10 µg/ml) auranofin triggered slight hemolysis (from 2.1 ± 0.2 to 3.2 ± 0.3%).
  
  
  CONCLUSIONS
  Auranofin stimulates cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least partially due to induction of oxidative stress.
authors.forename: Kousi
authors.initials: K
authors.lastname: Alzoubi
authors.forename: Jasmin
authors.initials: J
authors.lastname: Egler
authors.forename: Majed
authors.initials: M
authors.lastname: Abed
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D017304:Annexin A5 / Q000378:metabolism*; D017209:Apoptosis; D001310:Auranofin / Q000009:adverse effects* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D018384:Oxidative Stress; D010718:Phosphatidylserines / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D010718:Phosphatidylserines; D001310:Auranofin; D002118:Calcium