title: Effect of honokiol on erythrocytes.
abstract: Honokiol ((3,5-di-(2-propenyl)-1,1-biphenyl-2,2-diol), a component of Magnolia officinalis, stimulates apoptosis and is thus considered for the treatment of malignancy. In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and by breakdown of cell membrane phosphatidylserine asymmetry with phosphatidylserine-exposure at the erythrocyte surface. Eryptosis may be triggered following increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). The present study explored, whether honokiol elicits eryptosis. Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, hemolysis from hemoglobin release, [Ca(2+)]i from Fluo3-fluorescence, and ceramide from fluorescent antibodies. As a result, a 48 h exposure to honokiol was followed by a slight but significant increase of [Ca(2+)]i (15 μM), significant decrease of forward scatter (5 μM), significant increase of annexin-V-binding (5 μM) and significant increase of ceramide formation (15 μM). Honokiol further induced slight, but significant hemolysis. Honokiol (15 μM) induced annexin-V-binding was significantly blunted but not abrogated in the nominal absence of extracellular Ca(2+). In conclusion, honokiol triggers suicidal erythrocyte death or eryptosis, an effect at least in part due to stimulation of Ca(2+) entry and ceramide formation.
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstraße 5, 72076 Tuebingen, Germany.
authors.forename: Mohanad
authors.initials: M
authors.lastname: Zbidah
authors.forename: Adrian
authors.initials: A
authors.lastname: Lupescu
authors.forename: Tabea
authors.initials: T
authors.lastname: Herrmann
authors.forename: Wenting
authors.initials: W
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: Foller
authors.forename: Kashif
authors.initials: K
authors.lastname: Jilani
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D001713:Biphenyl Compounds / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000633:toxicity*; D010718:Phosphatidylserines / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D002118:Calcium; D017705:Lignans; D010718:Phosphatidylserines; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Calcium; Cell volume; Eryptosis; Honokiol; Phosphatidylserine