Volume 7 Supplement 2

13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT)

Open Access

Selective serotonin reuptake inhibitors: a new modality for the treatment of lymphoma/leukaemia?

  • Christian Schuster1,
  • Nora Fernbach2,
  • Uwe Rix2,
  • Giulio Superti-Furga2,
  • Marion Holy1,
  • Michael Freissmuth1Email author,
  • Harald H Sitte1 and
  • Veronika Sexl1
BMC Pharmacology20077(Suppl 2):A8

DOI: 10.1186/1471-2210-7-S2-A8

Published: 14 November 2007

Selective serotonin reuptake inhibitors (SSRIs) have recently been reported to specifically kill malignant cells of B-lymphoid origin. However, we found that all cell lines investigated underwent apoptotic cell death when exposed to SSRI concentrations exceeding 10 μM, regardless of whether the cell lines were derived from B- or T-lymphoid tumors or other sources. The structure-activity relationship readily distinguished the pro-apoptotic and growth-inhibitory effect of SSRIs from their eponymous action: acetylation of the SSRIs fluvoxamine and paroxetine abrogated the ability of these compounds to inhibit 5-HT uptake, but did not impair their cytotoxic action. Based on these data we conclude that (i) SSRIs inhibit growth of transformed cells, but that (ii) this effect is neither specific for malignant cells nor specific for any particular cellular subset. (iii) The pro-apoptotic effect of SSRIs (at μM concentrations) is unrelated to their principal pharmacological action, i.e. inhibition of serotonin uptake (at nM concentrations). SSRIs or improved versions thereof are therefore unlikely to represent useful lead compounds for inducing apoptosis in B-cell derived tumors.

Authors’ Affiliations

(1)
Department of Pharmacology, Center of Biomolecular Medicine and Pharmacology, Medical University of Vienna
(2)
Research Center for Molecular Medicine, Austrian Academy of Sciences

Copyright

© Schuster et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.

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