title: Fucoxanthin Induced Suicidal Death of Human Erythrocytes.
abstract: OBJECTIVE
  Fucoxanthin, a carotenoid isolated from brown seaweeds, induces suicidal death or apoptosis of tumor cells and is thus considered for the treatment or prevention of malignancy. In analogy to apoptosis of nucleated cell, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress and activation of p38 kinase or protein kinase C. The present study explored, whether and how fucoxanthin induces eryptosis.
  
  
  METHODS
  Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and abundance of reactive oxygen species (ROS) from DCFDA dependent fluorescence and lipid peroxidation using BODIPY fluoresence.
  
  
  RESULTS
  A 48 hours exposure of human erythrocytes to fucoxanthin significantly increased the percentage of annexin-V-binding cells (≥ 50 µM), significantly decreased average forward scatter (≥ 25 µM), significantly increased hemolysis (≥ 25 µM), significantly increased Fluo3-fluorescence (≥ 50 µM), significantly increased lipid peroxidation, but did not significantly modify DCFDA fluorescence. The effect of fucoxanthin on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+, and was insensitive to p38 kinase inhibitor skepinone (2 µM) and to protein kinase C inhibitor calphostin (100 nM).
  
  
  CONCLUSIONS
  Fucoxanthin triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of Ca2+ entry.
authors.forename: Marilena
authors.initials: M
authors.lastname: Briglia
authors.forename: Salvatrice
authors.initials: S
authors.lastname: Calabró
authors.forename: Elena
authors.initials: E
authors.lastname: Signoretto
authors.forename: Kousi
authors.initials: K
authors.lastname: Alzoubi
authors.forename: Stefan
authors.initials: S
authors.lastname: Laufer
authors.forename: Caterina
authors.initials: C
authors.lastname: Faggio
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D004789:Enzyme Activation; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D018384:Oxidative Stress; D024341:Xanthophylls / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D024341:Xanthophylls; C025164:fucoxanthin; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium