Evidence for Differential Effect of Two SSRIs Antidepressants on Murine Breast Cancer (4T1) in-Vitro and Tumor Grafted Female Mice under Normal and Stress Conditions

Background Breast cancer diagnosis and treatment are stressful events for most women, which often lead to severe depression. Antidepressants are widely prescribed to treat depression in cancer patients, However, no general consideration is applied regarding antidepressant selection. Previous results showed that some serotonin reuptake inhibitors (SSRIs), mainly Sertraline and Paroxetine demonstrated antiproliferative and apoptotic activity against several cell-lines in-vitro and colorectal tumor in xenografted mice, whereas other agents e.g Citalopram were not effective. Aims 1. Evaluation of the comparative effect of Sertraline and Citalopram on murine 4T1 breast cancer cell proliferation in- vitro and in-vivo 2. Determine the effect of stress and antidepressants therapy on 4T1 cell viability as well as on immune cells (splenocytes) viability and pro-inflammatory cytokine secretion. 3. Evaluate the comparative effect of the two SSRIs on tumor growth as well as on anxiety parameters in mice. Results In vitro, we found a marked difference between Sertraline and Citalopram. Sertraline induced a dose dependent inhibition of cell viability and splenocytes viability and proliferation. Whereas, Citalopram did not alter cell viability. In-vivo, chronic mild stress (CMS) induced anxiety in 4T1 grafted Balb/c mice model, however, it did not modify tumor growth. Sertraline but not Citalopram (10mg/kg/d each), deteriorated the animal`s physical condition inducing shortening of survival and increase in tumor growth. Conclusion Our results demonstrated a dissociation between the in vitro and the in vivo results, with Sertraline but not Citalopram, showing inhibitory effect in-vitro, and tumor accelerating activity at high dose in- vivo. Moreover, we could not demonstrate a deteriorating effect of our stress condition on tumor growth. We suggest that a careful approach should be taken regarding Sertraline therapy in patients.