Growth-inhibition of cell lines derived from B cell lymphomas through antagonism of serotonin receptor signaling

Abstract

A majority of lymphomas are derived from B cells and novel treatments are required to treat refractory disease. Neurotransmitters such as serotonin and dopamine influence activation of B cells and the effects of a selective serotonin 1A receptor (5HT1A) antagonist on growth of a number of B cell-derived lymphoma cell lines were investigated. We confirmed the expression of 5HT1A in human lymphoma tissue and in several well-defined experimental cell lines. We discovered that the pharmacological inhibition of 5HT1A led to the reduced proliferation of B cell-derived lymphoma cell lines together with DNA damage, ROS-independent caspase activation and apoptosis in a large fraction of cells. Residual live cells were found ‘locked’ in a non-proliferative state in which a selective transcriptional and translational shutdown of genes important for cell proliferation and metabolism occurred (e.g., AKT, GSK-3β, cMYC and p53). Strikingly, inhibition of 5HT1A regulated mitochondrial activity through a rapid reduction of mitochondrial membrane potential and reducing dehydrogenase activity. Collectively, our data suggest 5HT1A antagonism as a novel adjuvant to established cancer treatment regimens to further inhibit lymphoma growth.

B cells and the stressed brain: emerging evidence of neuroimmune interactions in the context of psychosocial stress and major depression

“…Some evidence in B cell and lymphoma lines suggests that SERT expression increases in activated B cells enabling them to take up 5HT ( Meredith et al, 2005 ) and transport it, potentially long distances. However, B cell-derived lymphoma cells failed to proliferate with 5HT stimulation and showed increased apoptosis with 5HT uptake ( Serafeim et al, 2002 ; Kolan et al, 2019 ). Interestingly, antidepressant intervention restores some B cell population numbers in MDD ( Hernandez et al, 2010 ; Ahmetspahic et al, 2018 ).…”