title: Fluoxetine regulates cell growth inhibition of interferon-α.
abstract: Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.
authors: Department of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C.
authors: Yu-Min
authors: YM
authors: Lin
authors: Departments of Animal Resource Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Bu-Chin
authors: BC
authors: Yu
authors: Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan, Taiwan, R.O.C.
authors: Wen-Tai
authors: WT
authors: Chiu
authors: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
authors: Hung-Yu
authors: HY
authors: Sun
authors: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
authors: Yu-Chieh
authors: YC
authors: Chien
authors: Department of Pharmacy, Chi-Mei Medical Center, Tainan, Taiwan, R.O.C.
authors: Hui-Chen
authors: HC
authors: Su
authors: Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, R.O.C.
authors: Shu-Yang
authors: SY
authors: Yen
authors: Department of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C.
authors: Hsin-Wen
authors: HW
authors: Lai
authors: Department of Public Health, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.
authors: Chyi-Huey
authors: CH
authors: Bai
authors: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
authors: Kung-Chia
authors: KC
authors: Young
authors: Department of Nursing, Chung Hwa University of Medical Technology, Tainan County, Taiwan, R.O.C.
authors: Chiung-Wen
authors: CW
authors: Tsao
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
chemical_list: D000998:Antiviral Agents; D005473:Fluoxetine; D016898:Interferon-alpha; D017367:Selective Serotonin Reuptake Inhibitors