Effects of triclocarban on the transcription of estrogen, androgen and aryl hydrocarbon receptor responsive genes in human breast cancer cells.

Abstract

Triclocarban (TCC) is an antimicrobial agent that is used in detergents, soaps and other personal hygiene products. Similarly to triclosan the widespread use of TCC has raised concerns about its endocrine potential. In luciferase-based reporter assays TCC has been shown to enhance estrogenic and androgenic activities following cellular coexposure with estrogen or dihydrotestosterone, respectively. The present study demonstrates that although coexposure with TCC enhances the estrogenic and androgenic readout of luciferase-based reporter cell lines such as HeLa9908 and MDA-kb2, it fails to act as a xenoandrogen on transcriptional level, nor does it induce cell proliferation in the estrogen sensitive E-screen. In addition TCC did not alter the expression of estrogen responsive genes in human mammary carcinoma MCF-7 cells exposed to 17β-estradiol, bisphenol A, butylparaben or genistein. However, TCC was shown to interfere with the regulon of the aryl hydrocarbon receptor (AhR) as TCC showed a costimulatory effect on transcription of CYP1A1 and CYP1B1, effectively lowering the transcriptional threshold for both genes in the presence of estrogens. It thus seems, that while the induction of the respective luciferase reporter assays by TCC is an unspecific false positive signal caused by luciferase stabilisation, TCC has the potential to interfere with the regulatory crosstalk of the estrogen receptor (ER) and the AhR regulon.

• Authors: Patrick Tarnow, Tewes Tralau, Danele Hunecke, Andreas Luch
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 27 Issue 5 Pg. 1467-75 (Aug 2013) ISSN: 1879-3177 [Electronic] England
• PMID: 23524099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Infective Agents, Local
• Carbanilides
• Estrogens
• Receptors, Androgen
• Receptors, Aryl Hydrocarbon
• Receptors, Estrogen
• triclocarban
• Luciferases
• Aryl Hydrocarbon Hydroxylases
• CYP1A1 protein, human
• CYP1B1 protein, human
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 CYP1B1

Topics

• Anti-Infective Agents, Local (pharmacology)
• Aryl Hydrocarbon Hydroxylases
• Biological Assay
• Breast Neoplasms
• Carbanilides (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 CYP1B1
• Estrogens (pharmacology)
• Female
• Gene Expression (drug effects)
• Genes, Reporter
• Humans
• Luciferases (genetics)
• Receptors, Androgen (genetics)
• Receptors, Aryl Hydrocarbon (genetics)
• Receptors, Estrogen (genetics)
• Transcription, Genetic