Fluoxetine-induced Apoptosis in Hepatocellular Carcinoma Cells

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. Materials and 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 Ca2+ chelator, prevented fluoxetine-induced modulation of MAPK. Conclusion: Fluoxetine appears to exhibit an apoptotic effect against Hep3B cells through the loss of MMP, formation of ROS and modulation of MAPK activities.