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

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

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 17 , Issue 11 , 2017

Become EABM
Become Reviewer

Graphical Abstract:


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.

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 17
ISSUE: 11
Year: 2017
Page: [1570 - 1577]
Pages: 8
DOI: 10.2174/1871520617666170327155930
Price: $58

Article Metrics

PDF: 27
HTML: 1
EPUB: 1