title: Triggering of Suicidal Erythrocyte Death Following Boswellic Acid Exposure.
abstract: OBJECTIVE
  The antinflammatory natural product boswellic acid is effective against cancer at least in part by inducing tumor cell apoptosis. Similar 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 erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca(2+)-activity ([Ca(2+)]i), energy depletion, ceramide formation and p38 kinase activation. The present study tested, whether and how boswellic acid induces eryptosis.
  
  
  METHODS
  Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca(2+)]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies, reactive oxygen species (ROS) from 2',7'-dichlorodihydrofuorescein diacetate (DCFDA) fluorescence, and cytosolic ATP concentration utilizing a luciferin-luciferase assay kit.
  
  
  RESULTS
  A 24 hours exposure of human erythrocytes to boswellic acid (5 µg/ml) significantly increased the percentage of annexin-V-binding cells (to 9.3 ± 0.9 %) and significantly decreased forward scatter. Boswellic acid did not significantly modify [Ca(2+)]i, cytosolic ATP, ROS, or ceramide abundance. The effect of boswellic acid on annexin-V-binding was significantly blunted, but not abolished by p38 kinase inhibitors skepinone (2 µM) and SB203580 (2 µM).
  
  
  CONCLUSIONS
  Boswellic acid stimulates cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part dependent on p38 protein kinase activity.
authors: Department of Physiology, University of Tx00FC;bingen, Tx00FC;bingen, Germany.
authors: Salvatrice
authors: S
authors: Calabrò
authors: Kousi
authors: K
authors: Alzoubi
authors: Caterina
authors: C
authors: Faggio
authors: Stefan
authors: S
authors: Laufer
authors: Florian
authors: F
authors: Lang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017304:Annexin A5 / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017304:Annexin A5; D002518:Ceramides; D006454:Hemoglobins; D007093:Imidazoles; D011725:Pyridines; D017382:Reactive Oxygen Species; D014315:Triterpenes; C054625:boswellic acid; D000255:Adenosine Triphosphate; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D002118:Calcium