5-Hydroxytryptamine drives apoptosis in biopsylike Burkitt lymphoma cells: reversal by selective serotonin reuptake inhibitors.

Serafeim A, Grafton G, Chamba A, Gregory CD, Blakely RD, Bowery NG, Barnes NM, Gordon J
Blood. 2002 99 (7): 2545-53

PMID: 11895792 · DOI:10.1182/blood.v99.7.2545

Serotonin (5-HT), a well-known neurotransmitter of the central nervous system, has been implicated in diverse aspects of immune regulation. Here we show that 5-HT can efficiently drive programmed cell death in established Burkitt lymphoma (BL) lines that remain faithful to the original biopsy phenotype (group 1). Group 1 BL cells cultured in the presence of 5-HT exhibited marked suppression of DNA synthesis that was accompanied by extensive apoptosis-serotonin-driven apoptosis was complete within 24 hours, was preceded by early caspase activation, and was accompanied by a decline in mitochondrial membrane potential. BL cells that had drifted to a lymphoblastic group 3 phenotype were relatively resistant to these actions of serotonin, and the forced ectopic expression of either bcl-2 or bcl-x(L) provided substantial protection from 5-HT-induced apoptosis. 5-HT receptor antagonists (SDZ205-557, granisetron, methysergide) failed to inhibit serotonin-induced apoptosis, whereas the selective serotonin reuptake inhibitors (SSRI)-fluoxetine (Prozac), paroxetine (Paxil), and citalopram (Celexa)-substantially blocked the monoamine actions. Western blot analysis showed that BL cells expressed protein for the 5-HT transporter, and transport assays confirmed active uptake of serotonin by the cells. Unlike what was suggested for neuronal cells, there was no evidence that intracellular oxidative metabolites were responsible for the 5-HT-induced programmed death of BL cells. These data indicate that serotonin drives apoptosis in biopsylike BL cells after its entry through an active transport mechanism, and they suggest a novel therapeutic modality for Burkitt lymphoma.

MeSH Terms (20)

Apoptosis Biopsy Blotting, Western Burkitt Lymphoma Carrier Proteins Caspases Cell Survival Citalopram DNA, Neoplasm DNA Damage Fluoxetine Humans Membrane Glycoproteins Membrane Transport Proteins Nerve Tissue Proteins Paroxetine Serotonin Serotonin Plasma Membrane Transport Proteins Serotonin Uptake Inhibitors Tumor Cells, Cultured

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