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Prepublished online as a Blood First Edition Paper on December 19, 2002; DOI 10.1182/blood-2002-07-2044. This Article Full Text (PDF) All Versions of this Article: 2002-07-2044v1 101/8/3212    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Serafeim, A. Articles by Gordon, J. Search for Related Content PubMed PubMed Citation Articles by Serafeim, A. Articles by Gordon, J. Social Bookmarking                   What's this? Submitted July 9, 2002 Accepted December 10, 2002 Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsylike Burkitt lymphoma cells Adamantios Serafeim, Michelle J Holder, Gillian Grafton, Anita Chamba, Mark T Drayson, Quang T Luong, Christopher M Bunce, Christopher D Gregory, Nicholas M Barnes, and John Gordon* MRC Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom Division of Medical Sciences, University of Birmingham Medical School, Birmingham, United Kingdom Division of Neurosciences, University of Birmingham Medical School, Birmingham, United Kingdom MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom * Corresponding author; email: j.gordon{at}bham.ac.uk. Selective serotonin reuptake inhibitors (SSRI) are the treatment of choice for clinical depression and a range of anxiety-related disorders. They are well tolerated over extended periods with more than 50 million people worldwide benefiting from their use. Here we show that three structurally distinct SSRI - fluoxetine (Prozac®), paroxetine (Paxil®), and citalopram (Celexa®) - act directly on Burkitt lymphoma (BL) cells to trigger rapid and extensive programmed cell death. SSRI unexpectedly stimulated calcium flux, tyrosine phosphorylation, and down-regulation of the c-myc and nm23 genes in Burkitt lymphoma cells remaining faithful to the biopsy phenotype. Resultant SSRI-induced apoptosis was preceded by caspase activation, PARP-1 cleavage, DNA fragmentation, a loss of mitochondrial membrane potential, the externalization of phosphatidylserine, and reversed by the over-expression of bcl-2. Normal peripheral blood mononuclear cells and tonsil B cells, whether resting or stimulated into cycle, were largely resistant to SSRI-induced death as were five non-BL lymphoid cell lines tested. We discuss these findings within the context of whether the SSRI class of antidepressants could find future application as potential therapeutics for the highly aggressive and - due to its association with AIDS - increasingly more common Burkitt lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Stebbing, T. Powles, S. Mandalia, M. Nelson, B. Gazzard, and M. Bower Use of Antidepressants and Risk of Cancer in Individuals Infected With HIV J. Clin. Oncol., May 10, 2008; 26(14): 2305 - 2310. [Abstract] [Full Text] [PDF] E. J. Meredith, M. J. Holder, A. Rosen, A. D. Lee, M. J. S. Dyer, N. M. Barnes, and J. Gordon Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin's lymphoma PNAS, September 5, 2006; 103(36): 13485 - 13490. [Abstract] [Full Text] [PDF] K. A. Blum, G. Lozanski, and J. C. Byrd Adult Burkitt leukemia and lymphoma Blood, November 15, 2004; 104(10): 3009 - 3020. [Abstract] [Full Text] [PDF] S. Bahl, M. Cotterchio, N. Kreiger, and N. Klar Antidepressant Medication Use and Non-Hodgkin's Lymphoma Risk: No Association Am. J. Epidemiol., September 15, 2004; 160(6): 566 - 575. [Abstract] [Full Text] [PDF]

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