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.