Abstract 2152: Paroxetine, a selective serotonin re-uptake inhibitor, induces growth inhibition and apoptosis in prostate cancer cells

Abstract

Abstract Introduction and Objective: Recently, neuroendocrine cells is suggested to be involved in prostate cancer (PC) progression through the secretion of a variety of neuroendocrine products, such as serotonin, which have mitogenic effects on adjacent cancer cells and thus can contribute to the androgen independent proliferation of PC cells. With having experience that a patient with hormone refractory prostate cancer responded to paroxetine, a selective serotonin re-uptake inhibitor (SSRI), in serum prostate specific antigen (PSA) level, we investigated the effect of paroxetine on the growth and apoptosis induction in PC cell lines. Methods: Paroxetine was administered to four patients with hormone refractory, metastatic PC and their serum PSA levels were determined. The effects of paroxetine on the growth and apoptosis induction in PC cell lines (PC3, DU145, 22RV1 and LNCaP) were confirmed. Cell growth inhibition was assessed in vitro by cell number count. The induction of apoptosis was examined by flow cytometry analysis and caspase activations were confirmed by western blot analysis. Results: Serum PSA levels decreased soon after the administration of paroxetine but increased again in all four patients but one in whom it decreased from 0.485 ng/ml to undetectable level (less than 0.008 ng/ml) for over three years. In vitro study, paroxetine inhibited cell growth in a dose and time dependent manner. The 50% inhibitory concentration (IC50 values) of paroxetine in PC3, 22RV1, DU145 and LNCaP cells were 38.8, 30.1, 35.9 and 21µM, respectively. Apoptosis induction following the treatment of paroxetine was revealed in prostate cancer cells by the increase of sub-G1 population in flow cytometry analysis and a cleavage of procaspase-3 in western blot analysis. Conclusions: A potent SSRI, paroxetine, induces growth inhibition and apoptosis in PC cells. These results suggest that SSRIs have the potential of anti-tumor effect against PC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2152. doi:10.1158/1538-7445.AM2011-2152