title: Fluoxetine-induced apoptosis in hepatocellular carcinoma cells.
abstract: BACKGROUND
  In addition to being used to treat mental disorders, a serious complication of cancer, antidepressants have been reported to improve cancer patient immunity, inhibit cell growth and have an antitumor effect on various cancer cell lines. We investigated the apoptotic effect of fluoxetine against the Hep3B human hepatocellular carcinoma cell line.
  
  
  METHODS
  After treatments of Hep3B cells with fluoxetine, we measured cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and activation of mitogen-activated protein kinases (MAPK).
  
  
  RESULTS
  Fluoxetine reduced the viability of cancer cells, induced loss of MMP and formation of ROS, reduced expression of extracellular signal-regulated kinase 1/2 and increased expression of c-JUN N-terminal kinase and p38 MAPK. N-Acetylcysteine, an oxidant-scavenger, and 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular Ca(2+) chelator, prevented fluoxetine-induced modulation of MAPK.
  
  
  CONCLUSIONS
  Fluoxetine appears to exhibit an apoptotic effect against Hep3B cells through the loss of MMP, formation of ROS and modulation of MAPK activities.
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, Chonbuk National University, Jeonju-561-756, Republic of Korea. abbasj@jbnu.ac.kr.
authors.forename: A-Reum
authors.initials: AR
authors.lastname: Mun
authors.forename: Sei-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Gi-Beum
authors.initials: GB
authors.lastname: Kim
authors.forename: Hyung-Sub
authors.initials: HS
authors.lastname: Kang
authors.forename: Jin-Shang
authors.initials: JS
authors.lastname: Kim
authors.forename: Shang-Jin
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D005473:Fluoxetine; D020782:Matrix Metalloproteinases; D020928:Mitogen-Activated Protein Kinases; D017382:Reactive Oxygen Species; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Fluoxetine; Hep3B cells; apoptosis; hepatocellular carcinoma; mitogen-activated protein kinase