Serotonin Transporter Found in B-Cell Malignancies: Inhibition of Cancer Growth by Inhibiting Transporter

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 8 No. 3 • July 2005


Serotonin Transporter Found in B-Cell Malignancies:
Inhibition of Cancer Growth by Inhibiting Transporter

The serotonin transporter (SERT) has recently1 been reported to be present in a large number of B-cell malignancies, including B-cell precursor acute lymphoblastic leukemia, multiple myeloma, Burkitt’s lymphoma, prolymphocytic leukemia, mantle-cell lymphoma, diffuse large B-cell lymphoma, and primary mediastinal B-cell lymphoma. Normal tonsilar B cells, however, contained no detectable SERT. Mitogenic stimulation (causing cells to divide) by phorbol ester, a known cancer promoter, and a calcium ionophore led to the induction of readily detectable SERT in resting B cells that otherwise had no detectable SERT.

The researchers then tested drugs that are known to target SERT, which include selective serotonin uptake inhibitors (the SSRI fluoxetine), the tricyclic antidepressant clomipramine, and the amphetamine derivatives MDMA (“Ecstasy”) and fenfluramine, to see whether they could arrest the growth of the model Burkitt’s lymphoma cell line. Twelve of the 17 derived B-cell lines showed an antiproliferative response to the tested psychotropics. Thus, as the authors note, this study establishes SERT expression as a phenotype common to neoplastic B-cell clones of widely distinct tumor origin.

The concentrations required for MDMA and fenfluramine to elicit an antitumor response were high. However, the effects of fluoxetine and clomipramine occurred at concentrations known to be reached in the serum of patients on standard dosing regimes for anxiety-related disorders; as these two agents pass the blood-brain barrier, the authors suggest that they be studied for the possible treatment of CNS lymphomas.

It is also interesting to note that the potent proinflammatory cytokine tumor necrosis factor-alpha enhances the function of the serotonin transporter,2 pointing out a possible mechanism for the depression associated with inflammation and/or cancer.

References

  1. Meredith et al. The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics. FASEB J 19:1187-9 (2005).
  2. Mossner et al. Enhancement of serotonin transporter function by tumor necrosis factor alpha but not by interleukin-6. Neurochem Int 33:251-4 (1998).

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