title: Anti-Cancer Effects of Citalopram on Hepatocellular Carcinoma Cells Occur via Cytochrome C Release and the Activation of NF-kB.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.|Students` Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Ahmadian
authors.affiliation: Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran.
authors.forename: Aziz
authors.initials: A
authors.lastname: Eftekhari
authors.affiliation: Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.|Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Babaei
authors.affiliation: Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Alireza M
authors.initials: AM
authors.lastname: Nayebi
authors.affiliation: Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.|Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Eghbal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D045304:Cytochromes c
keywords: Bay11-7082; Citalopram; HepG2.; apoptosis; cancer; cytotoxicity