Anti-Cancer Effects of Citalopram on Hepatocellular Carcinoma Cells Occur via Cytochrome C Release and the Activation of NF-kB.

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)κB 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 NFκB 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 NFκB.