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Growth-inhibition of cell lines derived from B cell lymphomas through antagonism of serotonin receptor signaling
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4276Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 9, article id 4276
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Cancer and Oncology
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URN: urn:nbn:se:umu:diva-157754DOI: 10.1038/s41598-019-40825-xISI: 000460924100016PubMedID: 30862884Scopus ID: 2-s2.0-85062839295OAI: oai:DiVA.org:umu-157754DiVA, id: diva2:1303116
Available from: 2019-04-08 Created: 2019-04-08 Last updated: 2019-04-08Bibliographically approved

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Kolan, Shrikant SLidström, TommyMediavilla, TomásDernstedt, AndyDegerman, SofieHultdin, MagnusMarcellino, DanielForsell, Mattias N. E.

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Kolan, Shrikant SLidström, TommyMediavilla, TomásDernstedt, AndyDegerman, SofieHultdin, MagnusMarcellino, DanielForsell, Mattias N. E.
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Immunology/ImmunchemistryDepartment of Integrative Medical Biology (IMB)Department of Medical Biosciences
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