Proapoptotic and chemosensitizing effects of selective serotonin reuptake inhibitors on T cell lymphoma/leukemia (Jurkat) in vitro Ben Hayman Amit a,b , Irit Gil-Ad a,b , Michal Taler a, ⁎ , Meytal Bar a,b , Amichai Zolokov a,b , Abraham Weizman a,b,c a Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel b Sackler Faculty of Medicine, Tel Aviv University, Israel c Research Unit, Geha Mental Health Center, Petah Tikva, Israel Received 9 March 2009; received in revised form 2 June 2009; accepted 9 June 2009 KEYWORDS Sertraline; Antidepressants; Chemosensitizers; Jurkat; T cell lymphoma; T cell leukemia Abstract While selective serotonin reuptake inhibitors (SSRIs) are commonly used for psychiatric indications, evidence implies them to possess anti-cancerous properties as well. We evaluated such in vitro effects in malignant T cells (Jurkat), finding that exposure to high concentrations of sertraline (IC 50 =9.5 μM) or paroxetine (IC 50 =18 μM) yielded a considerable reduction in cellular viability, exceeding equimolar doses of the chemotherapeutics vincristine and cyclophosphamide (P b 0.015). The cytotoxic effects included both inhibition of proliferation and induction of apoptosis, demonstrated by decreased [ 3 H] thymidine incorporation and increased activity of the caspase-3 enzyme, as well as a decrease in the expression of the Bcl-2 proto-oncogene. No effect on c-Jun or ERK was observed, rendering the complete mechanism yet to be fully elucidated. When combined with chemotherapy, sertraline (7.5 μM) markedly enhanced the effects of both vincristine and doxorubicin, suggesting SSRI antidepressants as potential new chemosensitizers in chemother- apeutic regimens, pending further in vivo research. © 2009 Elsevier B.V. and ECNP. All rights reserved. 1. Introduction Selective serotonin reuptake inhibitors (SSRIs) are antide- pressants commonly used for a number of psychiatric indications, mostly for depression and anxiety disorders (Sadock and Sadock, 2000). Their primary mechanism of action is relatively well understood, involving the inhibition ⁎ Corresponding author. Laboratory of Biological Psychaitry, Felsenstein Medical Research Center, Beilinson Campus, Petah Tikva 49100, Israel. Tel.: +972 3 9376783; fax: +972 3 9211478. E-mail address: michalt@post.tau.ac.il (M. Taler). 0924-977X/$ - see front matter © 2009 Elsevier B.V. and ECNP. All rights reserved. doi:10.1016/j.euroneuro.2009.06.003 www.elsevier.com/locate/euroneuro European Neuropsychopharmacology (2009) 19, 726–734