Differential effects of triclosan on the activation of mouse and human peroxisome proliferator-activated receptor alpha

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 (PPAR alpha) activation; however, the effects of triclosan on mouse and human PPARa have not been fully evaluated. We compared the effects of triclosan on mouse and human PPARa using PPARa reporter assays and on downstream events of PPARa activation using mouse hepatoma Hepa1c1c7 cells and human hepatoma HepG2 cells. PPARa transcriptional activity was increased by triclosan in a mouse PPARa reporter assay and decreased in a human PPARa 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 PPARa 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 PPARa, the expression of ACOX1, and downstream events including DNA synthesis and apoptosis. Published by Elsevier Ireland Ltd.