Archives of Toxicology

, Volume 89, Issue 8, pp 1297–1311 | Cite as

Extracellular signal-regulated kinases 1/2 and Akt contribute to triclosan-stimulated proliferation of JB6 Cl 41-5a cells

  • Yuanfeng Wu
  • Frederick A. Beland
  • Si Chen
  • Jia-Long FangEmail author
Molecular Toxicology


Triclosan is a broad spectrum anti-bacterial agent widely used in many personal care products, household items, medical devices, and clinical settings. Human exposure to triclosan is mainly through oral and dermal routes. In previous studies, we found that sub-chronic dermal exposure of B6C3F1 mice to triclosan induced epidermal hyperplasia and focal necrosis; however, the mechanisms for these responses remain elusive. In this study, using mouse epidermis-derived JB6 Cl 41-5a cells, we found that triclosan stimulated cell growth in a concentration- and time-dependent manner. Enhanced cell proliferation was demonstrated by a substantial increase in the percentage of BrdU-positive cells, an elevation in the protein levels of cyclin D1 and cyclin A, and a reduction in the protein level of p27Kip1. Western blotting analysis revealed that triclosan induced the activation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK), p38, and Akt. Pre-treatment of the cells with PD184352, an inhibitor of the upstream kinase MEK1/2, or with wortmannin, an inhibitor of phosphoinositide 3-kinase, blocked triclosan-mediated phosphorylation of ERK1/2 and Akt, respectively, and substantially suppressed triclosan-stimulated cell proliferation, whereas the JNK inhibitor SP600125 or the p38 inhibitor SB203580 had little to no effect on triclosan-stimulated cell proliferation. The phosphorylation activation of ERK1/2 and Akt was further confirmed on the skin of mice dermally administered triclosan. These data suggest that the activation of ERK1/2 and Akt is involved in triclosan-stimulated proliferation of JB6 Cl 41-5a cells.


Triclosan JB6 cells Cell proliferation Extracellular signal-regulated kinases 1/2 Akt 



Yuanfeng Wu and Si Chen were supported by an appointment to the Postgraduate Research in the Division of Biochemical Toxicology at the National Center for Toxicological Research administered by Oak Ridge Institute for Science Education through an interagency agreement between the U.S. Department of Energy and the U.S. FDA. This research was supported through an interagency agreement between the National Center for Toxicological Research, U.S. Food and Drug Administration (FDA) and the National Toxicology Program, National Institute of Environmental Health Sciences. (FDA IAG: 224-07-0007; NIH Y1ES1027).

Conflict of interest

The authors declare that there are no conflict of interests.


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Copyright information

© Springer 2014

Authors and Affiliations

  • Yuanfeng Wu
    • 1
  • Frederick A. Beland
    • 1
  • Si Chen
    • 1
  • Jia-Long Fang
    • 1
    Email author
  1. 1.Division of Biochemical Toxicology, National Center for Toxicological ResearchFood and Drug AdministrationJeffersonUSA

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