Abstract:
Alteration of epithelial cancer cell toward mesenchymal phenotype (epithelial-to-mesenchymal transition; EMT) has been shown to potentiate tumor aggressiveness by increasing cancer cell metastasis. Herein, the present study demonstrates the effect of triclosan, a widely used antibacterial agent found in many daily products, in enhancing the EMT in aggressive anoikis resistant human lung cancer cells. EMT was long known to increase abilities of cancer cells to increase migration and invasion as well as tumorigenicity of cells. The present study reveals that treatment of the anoikis resistant cells with triclosan at the physiologically-related concentrations significantly decreased cell to cell adhesion which is a dominant characteristic of cell undergoing EMT. Importantly, western blot analysis reveled 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, indicating mesenchymal phenotype of cells. Also, EMT-induced by triclosan treatment increased the colony number of the cancer cells assessed by tumor formation assay. 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 ability of the cells to migrate and invade. In conclusion, this study demonstrated that triclosan may potentiate tumorigenicity and motility of anoikis resistant human lung cancer cells 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.
