Triclosan Potentiates Epithelial-To-Mesenchymal Transition in Anoikis-Resistant Human Lung Cancer Cells

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.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

“…Commonly used in personal care products, triclosan and BPA ( 456 ), are endocrine disruptors ( 457–459 ) that are often detected in waters downstream in urban areas ( 460 , 461 ). In addition to immune evasion mechanisms ( 36 , 142 , 145 ), they interfere with wide spectrum of cancer-related mechanisms ( 36 , 173 , 429 , 462–464 ). DEHP ( 472 ) is also an endocrine disruptor ( 466 , 467 ) that can impact multiple hallmarks such as immune evasion, resistance to cell death, evasion of antiproliferative signaling, sustained proliferative signaling and tumor-promoting inflammation ( 36 , 288 , 468 , 469 ).…”

Zinc induces epithelial to mesenchymal transition in human lung cancer H460 cells via superoxide anion-dependent mechanism

“…However, indicators like the switching between E-cadherin and N-cadherin, as well as EMT transcription factors snail and slug are more acceptable as hallmarks of EMT [ 2 – 5 ]. In particular, lung cancer H460 cells were shown to undergo EMT in response to various stimuli [ 33 , 34 ]. EMT features of H460 cells were characterized by (i) the change of cell morphology from epithelial to fibroblast-liked mesenchymal shape, (ii) the increased EMT markers N-cadherin, vimentin, snail, and slug, together with the reduction of epithelial marker E-cadherin, and (iii) EMT behaviors, including increased migration, invasion and tumorigenic potential [ 33 – 38 ].…”

Triclosan exposure, transformation, and human health effects

“…TCS elevated proinflammatory cytokine expression of TNF-α and IL-6 in mouse liver (Yueh et al 2014). Many other in vitro studies suggested that TCS promotes cancer (Kim et al 2014; Lee et al 2014; Winitthana et al 2014; Wu et al 2015). Conversely, in other studies, investigators provided data suggesting that TCS may inhibit cancer development (Sadowski et al 2014; Deepa et al 2012; Schmid et al 2005).…”