Stimulation of suicidal erythrocyte death by trans-cinnamaldehyde

Trans-cinnamaldehyde, a component of leaves from Cinnamomum osmophloeum kaneh, has been shown to counteract tumor growth. The substance exerts its effect at least in part by triggering apoptosis. The propapoptotic signaling involves altered gene expression and mitochondrial depolarization. In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine-exposure at the cell surface. Triggers of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i). The present study explored, whether trans-cinnamaldehyde triggers eryptosis. Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin-V-binding, hemolysis from hemoglobin release, and [Ca2+]i from Fluo3-fluorescence. A 48 h exposure to trans-cinnamaldehyde (30 μM) significantly decreased forward scatter and increased annexin-V-binding, effects paralleled by increase of [Ca2+]i. Trans-cinnamaldehyde exposure was followed by a slight but significant increase of hemolysis. Removal of extracellular Ca2+ virtually abolished the effect of trans-cinnamaldehyde (30 μM) on annexin-V-binding. The present observations show that trans-cinnamaldehyde triggers suicidal death of erythrocytes, i.e. cells devoid of mitochondria and gene expression.