title: Differential effects of triclosan on the activation of mouse and human peroxisome proliferator-activated receptor alpha.
abstract: Triclosan is an anti-bacterial agent used in many personal care products, household items, medical devices, and clinical settings. Liver tumors occur in mice exposed to triclosan, a response attributed to peroxisome proliferator-activated receptor alpha (PPARα) activation; however, the effects of triclosan on mouse and human PPARα have not been fully evaluated. We compared the effects of triclosan on mouse and human PPARα using PPARα reporter assays and on downstream events of PPARα activation using mouse hepatoma Hepa1c1c7 cells and human hepatoma HepG2 cells. PPARα transcriptional activity was increased by triclosan in a mouse PPARα reporter assay and decreased in a human PPARα reporter assay. Concentrations of triclosan inhibiting 50% cell growth were similar in both human and mouse hepatoma cells. Western blotting analysis showed that triclosan increased acyl-coenzyme A oxidase (ACOX1), a PPARα target, in Hepa1c1c7 cells but decreased the level in HepG2 cells. Treatment of Hepa1c1c7 cells with triclosan enhanced DNA synthesis and suppressed transforming growth factor beta-mediated apoptosis. This did not occur in HepG2 cells. These data demonstrate that triclosan had similar cytotoxicity in Hepa1c1c7 and HepG2 cells, but differential effects on the activation of PPARα, the expression of ACOX1, and downstream events including DNA synthesis and apoptosis.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, HFT-110, Jefferson, AR 72079, USA.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, HFT-110, Jefferson, AR 72079, USA.
authors.forename: Qiangen
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, HFT-110, Jefferson, AR 72079, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Beland
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, HFT-110, Jefferson, AR 72079, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Ge
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Mugimane G
authors.initials: MG
authors.lastname: Manjanatha
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, HFT-110, Jefferson, AR 72079, USA. Electronic address: jia-long.fang@fda.hhs.gov.
authors.forename: Jia-Long
authors.initials: JL
authors.lastname: Fang
mesh_terms: D042962:Acyl-CoA Oxidase / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014260:Triclosan / Q000633:toxicity*
chemical_list: D000900:Anti-Bacterial Agents; D047493:PPAR alpha; D016212:Transforming Growth Factor beta; D014260:Triclosan; D042962:Acyl-CoA Oxidase
keywords: Apoptosis; DNA synthesis; PPARα; Triclosan