Details

Autor(en) / Beteiligte

• Bissinger, Rosi
• Bouguerra, Ghada
• Stockinger, Katja
• Abbès, Salem
• Lang, Florian

Titel

Triggering of Suicidal Erythrocyte Death by Topotecan

Ist Teil von

• Cellular physiology and biochemistry, 2015-01, Vol.37 (4), p.1607-1618

Ort / Verlag

Basel, Switzerland: Karger

Erscheinungsjahr

2015

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Background/Aims: The topoisomerase I inhibitor topotecan is used as treatment of various malignancies. The substance is effective by triggering tumor cell apoptosis. In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the outer face of the erythrocyte membrane. Signaling leading to eryptosis include Ca2+-entry and ceramide formation. The present study explored, whether and how topotecan induces eryptosis. Methods: Phosphatidylserine abundance at the erythrocyte surface was estimated from annexin V binding, cell volume from forward scatter, and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to topotecan significantly increased the percentage of annexin-V-binding cells and significantly decreased forward scatter. The effect of topotecan was paralleled by a significant increase of ceramide abundance. The effect of topotecan on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusions: Topotecan stimulated cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect paralleled by increase of ceramide abundance and partially dependent on entry of extracellular Ca2+.