TY - JOUR
T1 - Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells
AU - [No Value], [No Value]
AU - Holder, Michelle
AU - Grafton, Gillian
AU - Chamba, Anita
AU - Drayson, Mark
AU - Luong, Quang
AU - Bunce, Christopher
AU - Gregory, CD
AU - Barnes, Nicholas
AU - Gordon, John
PY - 2003/4/15
Y1 - 2003/4/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037944059&partnerID=8YFLogxK
U2 - 10.1182/blood-2002-07-2044
DO - 10.1182/blood-2002-07-2044
M3 - Article
SN - 1528-0020
VL - 101
SP - 3212
EP - 3219
JO - Blood
JF - Blood
IS - 8
ER -