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

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

Volume: 17 Issue: 11

Author(s): Elham Ahmadian , Aziz Eftekhari , Hossein Babaei , Alireza M. Nayebi and Mohammad A. Eghbal*

Affiliation:

• Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Postal Code 51664-14766, Tabriz,Iran

Keywords: Citalopram, cancer, apoptosis, Bay11-7082, cytotoxicity, HepG2.

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)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.

Cite this article as:

Ahmadian Elham , Eftekhari Aziz , Babaei Hossein , Nayebi M. Alireza and Eghbal A. Mohammad *, Anti-Cancer Effects of Citalopram on Hepatocellular Carcinoma Cells Occur via Cytochrome C Release and the Activation of NF-kB, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (11) . https://dx.doi.org/10.2174/1871520617666170327155930