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Complex Effects of Sertraline and Citalopram on In Vitro Murine Breast Cancer Proliferation and on In Vivo Progression and Anxiety Level
Authors:Michal Taler  Irit Gil-Ad  Iris Brener  Shay Henry Hornfeld  Abraham Weizman
Affiliation:1.Laboratory of Biological and Molecular Psychiatry, Felsenstein Medical Research Center, 39 Jabotinski St., Petah Tikva 4941492, Israel; (M.T.); (I.G.-A.); (I.B.); (S.H.H.);2.Petah Tikva and Department of Psychiatry, Sackler Faculty of Medicine, Tel Aviv University, 35 Klachkin St., Tel Aviv 6997801, Israel;3.Research Unit, Geha Mental Health Center, 1 Helsinki St., Petah Tikva 4910002, Israel
Abstract:Some selective serotonin reuptake inhibitors (SSRIs), primarily sertraline, demonstrate anti-proliferative activity in malignant cell-lines and in xenografted mouse models of colorectal tumor. There is, however, a paucity of comparative studies on the anti-tumor effects of SSRIs. We compared the in vitro and in vivo effects of sertraline and citalopram on murine 4T1 breast cancer. Grafted mice were used to determine the rate of tumor growth and survival as well as the impact of stress and antidepressant treatment on tumor progression and mortality and on pro-inflammatory cytokines. Sertraline, in the micromolar range, but not citalopram, induced a significant in vitro concentration-dependent inhibition of murine 4T1 cell proliferation and splenocyte viability. In contrast, sertraline (10 mg/kg/d), enhanced in vivo tumor growth. Contrary to the study’s hypothesis, chronic mild stress did not modify tumor growth in grafted mice. The in vitro effects of sertraline on tumor growth seem to be the opposite of its in vivo effects. The impact of sertraline treatment on humans with breast cancer should be further investigated.
Keywords:antidepressants  SSRIs  breast cancer  stress  tumor growth  oncological pharmacology
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