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

[ Vol. 17 , Issue. 11 ]

Author(s):

Elham Ahmadian , Aziz Eftekhari , Hossein Babaei , Alireza M. Nayebi and Mohammad A. Eghbal*   Pages 1570 - 1577 ( 8 )

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.

Keywords:

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

Affiliation:

Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Postal Code 51664-14766, Tabriz

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