title: Triggering of suicidal erythrocyte death by celecoxib.
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.
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstraße 5, Tuebingen 72076, Germany. florian.lang@uni-tuebingen.de.
authors.forename: Adrian
authors.initials: A
authors.lastname: Lupescu
authors.forename: Rosi
authors.initials: R
authors.lastname: Bissinger
authors.forename: Kashif
authors.initials: K
authors.lastname: Jilani
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D000068579:Celecoxib; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D010718:Phosphatidylserines; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D002118:Calcium
references.citation: Cell Death Differ. 2005 May;12(5):415-28
references.pmid: 15746942
references.citation: Cell Physiol Biochem. 2011;28(6):1279-86
references.pmid: 22179015
references.citation: Future Med Chem. 2012 Mar;4(3):361-83
references.pmid: 22393942
references.citation: J Am Soc Nephrol. 2003 Nov;14(11):2750-7
references.pmid: 14569084
references.citation: Br J Haematol. 1999 Nov;107(2):300-2
references.pmid: 10583215
references.citation: Cell Physiol Biochem. 2009;24(5-6):415-28
references.pmid: 19910682
references.citation: Neurosurg Focus. 2006 Apr 15;20(4):E21
references.pmid: 16709027
references.citation: IUBMB Life. 2008 Oct;60(10):661-8
references.pmid: 18720418
references.citation: J Membr Biol. 2012 Dec;245(12):797-805
references.pmid: 22836670
references.citation: Cell Physiol Biochem. 2011;28(5):857-64
references.pmid: 22178938
references.citation: Cell Calcium. 2012 Jan;51(1):51-6
references.pmid: 22197026
references.citation: FASEB J. 2001 Jul;15(9):1622-4
references.pmid: 11427506
references.citation: J Clin Invest. 1993 Jul;92(1):520-6
references.pmid: 8326017
references.citation: J Proteome Res. 2011 Apr 1;10(4):1690-7
references.pmid: 21214270
references.citation: Cell Physiol Biochem. 2012;30(3):678-86
references.pmid: 22854627
references.citation: Int J Biochem Cell Biol. 2012 Aug;44(8):1236-43
references.pmid: 22561748
references.citation: Cell Physiol Biochem. 2003;13(6):347-56
references.pmid: 14631141
references.citation: J Nat Prod. 2012 Apr 27;75(4):531-7
references.pmid: 22483064
references.citation: Basic Clin Pharmacol Toxicol. 2012 Nov;111(5):348-55
references.pmid: 22726235
references.citation: Int J Nanomedicine. 2013;8:2173-86
references.pmid: 23807846
references.citation: Nat Med. 2007 Feb;13(2):164-70
references.pmid: 17259995
references.citation: Oncology (Williston Park). 2002 Apr;16(4 Suppl 3):17-21
references.pmid: 12014863
references.citation: Cell Death Differ. 2001 Dec;8(12):1197-206
references.pmid: 11753567
references.citation: Cell Physiol Biochem. 2009;24(3-4):133-40
references.pmid: 19710527
references.citation: J Cardiometab Syndr. 2008 Winter;3(1):30-4
references.pmid: 18326983
references.citation: Cell Physiol Biochem. 2006;18(4-5):223-32
references.pmid: 17167227
references.citation: Exp Diabetes Res. 2012;2012:316384
references.pmid: 22611373
references.citation: J Cell Biochem. 2012 May;113(5):1581-9
references.pmid: 22174104
references.citation: Curr Opin Hematol. 1999 Mar;6(2):76-82
references.pmid: 10088636
references.citation: Cell Physiol Biochem. 2011;27(1):45-54
references.pmid: 21325821
references.citation: Toxins (Basel). 2013 Apr 19;5(4):703-16
references.pmid: 23604064
references.citation: Cell Physiol Biochem. 2010;26(6):859-68
references.pmid: 21220917
references.citation: Am J Physiol Cell Physiol. 2003 Dec;285(6):C1553-60
references.pmid: 14600080
references.citation: Open Rheumatol J. 2012;6:44-9
references.pmid: 22629288
references.citation: Toxicology. 2012 Mar 29;294(1):54-60
references.pmid: 22330256
references.citation: Acta Diabetol. 2013 Aug;50(4):489-95
references.pmid: 21437568
references.citation: Pflugers Arch. 2004 Aug;448(5):471-7
references.pmid: 15156318
references.citation: Cell Physiol Biochem. 2010;26(3):347-54
references.pmid: 20798519
references.citation: Cell Physiol Biochem. 2011;28(2):347-54
references.pmid: 21865743
references.citation: Prog Clin Biol Res. 1987;240:193-200
references.pmid: 2441414
references.citation: Blood. 2003 Jun 1;101(11):4625-7
references.pmid: 12560240
references.citation: Kidney Blood Press Res. 2012;36(1):107-18
references.pmid: 23095759
references.citation: J Mol Med (Berl). 2007 Mar;85(3):273-81
references.pmid: 17180345
references.citation: Cell Biochem Biophys. 2013 Mar;65(2):145-57
references.pmid: 22903352
references.citation: Cancer Detect Prev. 2004;28(2):127-42
references.pmid: 15068837
references.citation: Nanotoxicology. 2012 Dec;6:847-56
references.pmid: 22022996
references.citation: J Physiol Pharmacol. 2009 Sep;60(3):135-43
references.pmid: 19826192
references.citation: Am J Physiol Cell Physiol. 2006 Jan;290(1):C244-53
references.pmid: 16338977
references.citation: Cell Physiol Biochem. 2009;23(1-3):191-8
references.pmid: 19255513
references.citation: J Cell Physiol. 2007 Dec;213(3):699-709
references.pmid: 17516566
references.citation: Blood Purif. 2012;34(3-4):209-10; author reply 210
references.pmid: 23095711
references.citation: Cell Physiol Biochem. 2010;26(3):355-62
references.pmid: 20798520
references.citation: Cell Physiol Biochem. 2012;30(4):876-88
references.pmid: 22907570
references.citation: Toxins (Basel). 2013 Jul 15;5(7):1230-43
references.pmid: 23860350
references.citation: Cell Physiol Biochem. 2012;30(1):282-94
references.pmid: 22759974
references.citation: Cell Mol Life Sci. 2005 May;62(9):971-88
references.pmid: 15761668
references.citation: Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):414-21
references.pmid: 17110600
references.citation: Cell Physiol Biochem. 2008;22(5-6):373-80
references.pmid: 19088418
references.citation: Cancer Lett. 2012 Sep 1;322(1):35-44
references.pmid: 22343223
references.citation: FASEB J. 2009 Apr;23(4):1072-80
references.pmid: 19050047
references.citation: Cell Physiol Biochem. 2012;30(4):863-75
references.pmid: 22907543
references.citation: FASEB J. 2006 Feb;20(2):368-70
references.pmid: 16371427
references.citation: Am J Physiol Cell Physiol. 2012 Feb 15;302(4):C644-51
references.pmid: 22173866
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6771-6
references.pmid: 18443297
references.citation: Blood Purif. 2012;33(1-3):125-30
references.pmid: 22269222
references.citation: Blood. 1996 Sep 1;88(5):1873-80
references.pmid: 8781447
references.citation: Mol Cell Biochem. 2011 Nov;357(1-2):171-9
references.pmid: 21625956
references.citation: J Mol Med (Berl). 2006 May;84(5):378-88
references.pmid: 16622713
references.citation: Drug Chem Toxicol. 2012 Oct;35(4):456-62
references.pmid: 22168270
references.citation: Cell Physiol Biochem. 2008;21(1-3):183-92
references.pmid: 18209485
references.citation: Ann Pharmacother. 2005 Jun;39(6):1138
references.pmid: 15840730
references.citation: Cell Physiol Biochem. 2010;26(1):21-8
references.pmid: 20502001
references.citation: PLoS One. 2012;7(3):e33774
references.pmid: 22438997
references.citation: Cell Physiol Biochem. 2012;30(3):512-22
references.pmid: 22814298
references.citation: Cell Physiol Biochem. 2011;27(5):547-56
references.pmid: 21691072
references.citation: Cell Physiol Biochem. 2011;27(5):557-64
references.pmid: 21691073
references.citation: Cancer Lett. 2013 May 28;332(2):313-24
references.pmid: 21345578
references.citation: Cell Physiol Biochem. 2011;28(2):339-46
references.pmid: 21865742
references.citation: Arch Toxicol. 2012 May;86(5):741-52
references.pmid: 22349056