The polyphenolic
1,2,3,4,6-penta-O-galloyl-beta-D-glucose from several medicinal herbs triggers apoptosis and has, thus, been proposed for treatment of
malignancy. The substance is at least partially effective through
caspase activation. In analogy to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by
phosphatidylserine translocation to the erythrocyte surface. Eryptosis is triggered by increase of cytosolic Ca2+-activity ([Ca2+]i). The sensitivity to [Ca2+]i is enhanced by
ceramide. The present study explored whether
penta-O-galloyl-β-
D-glucose stimulates eryptosis. Cell volume was estimated from forward scatter,
phosphatidylserine exposure from
annexin V binding,
hemolysis from
hemoglobin-release, [Ca2+]i from Fluo3-fluorescence and
ceramide abundance from fluorescent
antibodies. A 48-h exposure of human erythrocytes to
penta-O-galloyl-β-
D-glucose significantly decreased forward scatter (50 µM) and significantly increased
annexin V binding (10 µM). Up to 50 µM
penta-O-galloyl-β-
D-glucose did not significantly modify [Ca2+]i. However, the effect of
penta-O-galloyl-β-
D-glucose (25 µM) induced
annexin V binding was slightly, but significantly, blunted by removal of extracellular Ca2+, pointing to sensitization of erythrocytes to the scrambling effect of Ca2+.
Penta-O-galloyl-β-
D-glucose (25 µM) further increased
ceramide formation. In conclusion,
penta-O-galloyl-β-
D-glucose stimulates suicidal erythrocyte death or eryptosis, an effect partially due to stimulation of
ceramide formation with subsequent sensitization of erythrocytes to Ca2+.