Anti-cancer effects of citalopram on hepatocellular carcinoma cells occur via cytochrome C release and the activation of NF-?B

Abstract

Background: Evidence has been provided of the anti-proliferative activity of citalopram against some cancer cells. Objective: The apoptotic impact of citalopram, an antidepressant, against liver hepatocellular carcinoma cell line HepG2 was investigated in relation to the oxidative pathway and nuclear factor (NF)?B activation. Method: The cytotoxic effects of citalopram on HepG2 cells were determined by MTT assay. Reactive oxygen species (ROS) formation and cytochrome c release were measured following treatment with citalopram. Apoptosis analysis and Bax and Bcl--?2 mRNA and protein levels were also determined. Results: The cytotoxic effects of different concentrations of citalopram on HepG2 cells were observed as a reduction in cell viability and an increase in ROS formation. Citalopram caused an increase in mitochondrial Bax levels and a decrease in Bcl2 levels and also caused cytochrome c release. Moreover, DAPI staining and flow cytometry assays revealed citalopram-induced apoptosis in HepG2 cells. Oxidant scavengers and Bay 11-7082 (an irreversible inhibitor of NF?B activation) prevented the citalopram-associated cell death, increased BAX and decreased Bcl2. Conclusion: Outcomes from current study suggest that citalopram might exhibit apoptotic effect against hepatocellular carcinoma cell line by induction of cell death through cytochrome c release and ROS-dependent activation of NF?B. é 2017 Bentham Science Publishers.