Complex Effects of Sertraline and Citalopram on In Vitro Murine Breast Cancer Proliferation and on In Vivo Progression and Anxiety Level

Michal Taler,Abraham Weizman,Iris Brener,Shay Henry Hornfeld,Irit Gil-Ad

doi:10.3390/ijms23052711

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.

Highlights

The comparative in vitro anti-proliferative effect of sertraline and citalopram on the murine breast cancer 4T1 cell-line, growth and survival, the in vivo interaction among selective serotonin reuptake inhibitors (SSRIs), stress and tumor progression in a mouse 4T1 breast cancer grafted model and ex-vivo splenocyte proliferation, and secretion of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α, in response to LPS stimulation, which may affect cancer progression. In this series of experiments we compared the anti-proliferative effects of sertraline, which, as mentioned above, we have shown to possess anti-proliferative properties and citalopram, which we have shown not to possess such properties [10]
The effects of various concentrations of sertraline and citalopram on the viability of the 4T1 murine mammary carcinoma cell-line, as determined by the Neutral Red method were studied for 24 h under normal conditions
This study provides evidence that the administration of 10 mg/kg/d of the antidepressant sertraline, but not citalopram, to breast cancer inoculated female mice may accelerate tumor growth and cancer progression