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Triggering of Suicidal Erythrocyte Death by Celecoxib
Department of Physiology, University of Tuebingen, Gmelinstraße 5, Tuebingen 72076, Germany
* Author to whom correspondence should be addressed.
Received: 19 August 2013; in revised form: 3 September 2013 / Accepted: 4 September 2013 / Published: 10 September 2013
Abstract: The selective cyclooxygenase-2 (COX-2) inhibitor celecoxib triggers apoptosis of tumor cells and is thus effective against malignancy. The substance is at least partially effective through mitochondrial depolarization. Even though lacking mitochondria, erythrocytes may enter apoptosis-like suicidal death or eryptosis, which is characterized by cell shrinkage and by phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be triggered by increase of cytosolic Ca2+-activity ([Ca2+]i). The present study explored whether celecoxib stimulates eryptosis. Forward scatter was determined to estimate cell volume, annexin V binding to identify phosphatidylserine-exposing erythrocytes, hemoglobin release to depict hemolysis, and Fluo3-fluorescence to quantify [Ca2+]i. A 48 h exposure of human erythrocytes to celecoxib was followed by significant increase of [Ca2+]i (15 µM), significant decrease of forward scatter (15 µM) and significant increase of annexin-V-binding (10 µM). Celecoxib (15 µM) induced annexin-V-binding was blunted but not abrogated by removal of extracellular Ca2+. In conclusion, celecoxib stimulates suicidal erythrocyte death or eryptosis, an effect partially due to stimulation of Ca2+ entry.
Keywords: cell membrane scrambling; phosphatidylserine; calcium; cell volume; eryptosis
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MDPI and ACS Style
Lupescu, A.; Bissinger, R.; Jilani, K.; Lang, F. Triggering of Suicidal Erythrocyte Death by Celecoxib. Toxins 2013, 5, 1543-1554.
Lupescu A, Bissinger R, Jilani K, Lang F. Triggering of Suicidal Erythrocyte Death by Celecoxib. Toxins. 2013; 5(9):1543-1554.
Lupescu, Adrian; Bissinger, Rosi; Jilani, Kashif; Lang, Florian. 2013. "Triggering of Suicidal Erythrocyte Death by Celecoxib." Toxins 5, no. 9: 1543-1554.