Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells

[No Value] [No Value], Michelle Holder, Gillian Grafton, Anita Chamba, Mark Drayson, Quang Luong, Christopher Bunce, CD Gregory, Nicholas Barnes, John Gordon

Research output: Contribution to journalArticle

130 Citations (Scopus)


Selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for clinical depression and a range of anxiety-related disorders. They are well tolerated over extended periods I with more than 50 million people worldwide benefiting from their use. Here we show that 3 structurally distinct SSRI-fluoxetine, paroxetine, and citalopram-act directly on Burkitt lymphoma (BL) cells to trigger rapid and extensive programmed cell death. SSRIs 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, poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, DNA fragmentation; a. loss of mitochondrial membrane potential, And the externalization of phosphatidylserine, and reversed by the overexpression of bcl-2. Normal peripheral blood monoinuclear cells and tonsil B cells, whether resting or stimulated into cycle, Were largely resistant to SSRI-induced death as. Were 5 non-BL lymohoid cell lines tested. We discuss these findings within the context of whether the SSRI class of antideoressants could find future application as potential therapeutics for the highly aggressive and-because of its association with AIDS-Increasingly more common Burikitt lymphoma. (C) 2003 by The American Society of Hematology.
Original languageEnglish
Pages (from-to)3212-3219
Number of pages8
Issue number8
Early online date19 Dec 2002
Publication statusPublished - 15 Apr 2003


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