Triclosan potentiates epithelial-to-mesenchymal transition in anoikis-resistant human lung cancer cells

PLoS One. 2014 Oct 16;9(10):e110851. doi: 10.1371/journal.pone.0110851. eCollection 2014.

Abstract

Alteration of cancer cell toward mesenchymal phenotype has been shown to potentiate tumor aggressiveness by increasing cancer cell metastasis. Herein, we report the effect of triclosan, a widely used antibacterial agent found in many daily products, in enhancing the epithelial-to-mesenchymal transition (EMT) in aggressive anoikis resistant human H460 lung cancer cells. EMT has been long known to increase abilities of the cells to increase migration, invasion, and survival in circulating system. The present study reveals that treatment of the cancer cells with triclosan at the physiologically related concentrations significantly increased the colony number of the cancer cells assessed by tumor formation assay. Also, the mesenchymal-like morphology and decrease in cell-to-cell adhesion were observed in triclosan-treated cells. Importantly, western blot analysis revealed that triclosan-treated cells exhibited decreased E-cadherin, while the levels of EMT markers, namely N-cadherin, vimentin, snail and slug were found to be significantly up-regulated. Furthermore, EMT induced by triclosan treatment was accompanied by the activation of focal adhesion kinase/ATP dependent tyrosine kinase (FAK/Akt) and Ras-related C3 botulinum toxin substrate 1 (Rac1), which enhanced the ability of the cells to migrate and invade. In conclusion, we demonstrated for the first time that triclosan may potentiate cancer cells survival in detached condition and motility via the process of EMT. As mentioned capabilities are required for success in metastasis, the present study provides the novel toxicological information and encourages the awareness of triclosan use in cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anoikis / genetics*
  • Cadherins / biosynthesis
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Pseudopodia / genetics
  • Pseudopodia / pathology
  • Signal Transduction / drug effects
  • Triclosan / administration & dosage*
  • Vimentin / biosynthesis

Substances

  • Cadherins
  • Vimentin
  • Triclosan

Grant support

This research was supported by the Thailand Research Fund (to PC) (http://www.trf.or.th), Ratchadaphiseksomphot Endowment Fund of Chulalongkorn University (RES560530132-HR), the 90th Anniversary of Chulalongkorn University Fund (Ratchadapiseksomphot Endowment Fund), and the Chulalongkorn University Graduate Scholarship to Commemorate the 72nd Anniversary of His Majesty King Bhumibol Adulyadej (http://www.grad.chula.ac.th/eng/scholarships). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.