title: Programmed erythrocyte death following in vitro Treosulfan treatment.
abstract: OBJECTIVE
  The cytotoxic drug Treosulfan is clinically used for the treatment of malignancy. A common side effect of Treosulfan treatment is anemia. Treosulfan is at least partially effective by triggering apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and translocation of phosphatidylserine from the inner to the outer leaflet of the plasma membrane. Triggers of eryptosis include oxidative stress, Ca(2+)-entry and increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). The present study explored whether Treosulfan stimulates eryptosis, which may contribute to development of anemia.
  
  
  METHODS
  Erythrocyte volume was estimated from forward scatter, phosphatidylserine abundance at the erythrocyte surface from Fluorescein isothiocyanate (FITC)-annexin-V-binding, [Ca(2+)]i from Fluo3 fluorescence and reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA)-fluorescence.
  
  
  RESULTS
  A 48 hours exposure of human erythrocytes to Treosulfan (800 µg/ml) significantly decreased erythrocyte forward scatter, increased the percentage of annexin-V-binding cells, increased [Ca(2+)]i, and increased ROS. The effect of Treosulfan on annexin-V-binding was virtually abrogated by removal of extracellular Ca(2+).
  
  
  CONCLUSIONS
  Treosulfan stimulates suicidal erythrocyte death or eryptosis at least in part by inducing oxidative stress and stimulating Ca(2+) entry.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Peter
authors.forename: Rosi
authors.initials: R
authors.lastname: Bissinger
authors.forename: Sigrid
authors.initials: S
authors.lastname: Enkel
authors.forename: Kousi
authors.initials: K
authors.lastname: Alzoubi
authors.forename: Gergely
authors.initials: G
authors.lastname: Oswald
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002066:Busulfan / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014966:Xanthenes / Q000737:chemistry
chemical_list: D000814:Aniline Compounds; D018906:Antineoplastic Agents, Alkylating; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D014966:Xanthenes; C059715:Fluo-3; C018404:treosulfan; D002066:Busulfan; D016650:Fluorescein-5-isothiocyanate; D002118:Calcium