Growth-inhibition of cell lines derived from B cell lymphomas through antagonism of serotonin receptor signaling.
Sci Rep
; 9(1): 4276, 2019 03 12.
Article
in En
| MEDLINE
| ID: mdl-30862884
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-3ß, 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Lymphoma, B-Cell
/
Receptors, Serotonin
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Humans
/
Middle aged
Language:
En
Journal:
Sci Rep
Year:
2019
Document type:
Article
Affiliation country:
Sweden