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- Title
Triggering of Suicidal Erythrocyte Death by Topotecan.
- Authors
Bissinger, Rosi; Bouguerra, Ghada; Stockinger, Katja; abbès, Salem; Lang, Florian
- Abstract
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+. © 2015 S. Karger AG, Basel
- Subjects
DNA topoisomerase I; DNA topoisomerase inhibitors; TOPOTECAN; PHOSPHATIDYLSERINES; CERAMIDES
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2015, Vol 37, Issue 4, p1607
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000438527