Long‐term exposure to triclosan increases migration and invasion of human breast epithelial cells in vitro

• Published in: Journal of applied toxicology 2021-07, Vol.41 (7), p.1115-1126
• Main Authors: Farasani, Abdullah, Darbre, Philippa D.
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents, Local - toxicity; Antigens, CD; Antiinfectives and antibacterials; Antimicrobial agents; Breast cancer; Breast milk; Cadherins - genetics; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Consumer products; Epithelial cells; Epithelial Cells - metabolism; Epithelial-Mesenchymal Transition - drug effects; Epithelium; Estrogens; Estrogens - metabolism; Exposure; E‐cadherin; Gene Expression Regulation, Neoplastic; Human populations; Human tissues; Humans; Immunoblotting; invasion; MCF-7 Cells; Mesenchyme; Metastases; migration; motility; Neoplasm Invasiveness; Personal grooming; Polymerase chain reaction; Reduction; Reverse transcription; RNA, Messenger - genetics; Tissues; Triclosan; Triclosan - toxicity; Tumors; xCELLigence
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4097

Extensive use of triclosan (2,4,4′‐trichloro‐2′‐hydroxydiphenyl ether) as an antimicrobial agent in household and personal care products has resulted in global exposure of the human population. Its presence in human tissues, including milk, and its oestrogen‐disrupting properties raise concerns for an involvement in breast cancer. Because metastatic tumour spread is the main cause of breast cancer mortality, we have investigated the effects of triclosan on cell migration and invasion using three human breast epithelial cell lines and using concentrations comparable with those in human tissues. Long‐term exposure to 10−7 M of triclosan resulted in increased migration and invasion as measured by xCELLigence technology for all three cell lines, for the immortalized but nontransformed MCF‐10F breast epithelial cells (after 28 weeks), the oestrogen‐responsive MCF‐7 breast cancer cells (after 17 weeks) and the oestrogen‐unresponsive MDA‐MB‐231 breast cancer cells (after 20 weeks). The effects were therefore not limited to cancerous cells or to oestrogen‐responsive cells. This was paralleled in the MCF‐10F and MCF‐7 (but not MDA‐MB‐231) cells by a reduction in levels of E‐cadherin mRNA as measured by reverse transcription–polymerase chain reaction (RT‐PCR) and of E‐cadherin protein as measured by western immunoblotting, suggesting a mechanism involving epithelial‐to‐mesenchymal transition. This adds triclosan to the increasing list of ingredients of personal care products that can not only enter human breast tissue and increase cell proliferation but also influence cell motility. If mixtures of components in household and personal care products contribute to increasing cell migration and invasion, then reduction in exposure could offer a strategy for reducing breast cancer spread. Long‐term (>15 weeks) exposure to 10−7 M of triclosan resulted in increased migration and invasion of three human breast epithelial cell lines as measured using xCELLigence technology. Effects were not limited to cancerous cells or to oestrogen‐responsive cells. In two cell lines, reduced levels of E‐cadherin (mRNA and protein) were observed, suggesting a mechanism involving epithelial‐to‐mesenchymal transition. Triclosan is therefore another ingredient of personal care products that is entering the human breast and increasing cell motility, which is a prerequisite for metastasis.